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1. Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome†

Author: Dominique Burnouf, Florian Veillard, Anne-Marie Lobstein, Clément Monsarrat, Jean-Marc Reichhart, Camille Noûs, Guillaume Compain, Philippe Wolff, Gilles Guichard, Christophe André, Jérôme Wagner, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Modèles Insectes de l'Immunité Innée (M3I), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Cogitamus, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), and Wagner, Jerome
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, DNA polymerase, Peptide, medicine.disease_cause, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, Ribosome, 03 medical and health sciences, medicine, Molecular Biology, Escherichia coli, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, DNA clamp, biology, 030306 microbiology, Sciences du Vivant [q-bio]/Biotechnologies, Processivity, biology.organism_classification, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 3. Good health, Chemistry, chemistry, Chemistry (miscellaneous), biology.protein, Antibacterial activity, Bacteria
Abstract: The bacterial processivity factor, or sliding clamp (SC), is a target of choice for new antibacterial drugs development. We have previously developed peptides that target Escherichia coli SC and block its interaction with DNA polymerases in vitro. Here, one such SC binding peptide was fused to a Proline-rich AntiMicrobial Peptide (PrAMP) to allow its internalization into E. coli cells. Co-immunoprecipitation assays with a N-terminally modified bifunctional peptide that still enters the bacteria but fails to interact with the bacterial ribosome, the major target of PrAMPs, demonstrate that it actually interacts with the bacterial SC. Moreover, when compared to SC non-binding controls, this peptide induces a ten-fold higher antibacterial activity against E. coli, showing that the observed antimicrobial activity is linked to SC binding. Finally, an unmodified bifunctional compound significantly increases the survival of Drosophila melanogaster flies challenged by an E. coli infection. Our study demonstrates the potential of PrAMPs to transport antibiotics into the bacterial cytoplasm and validates the development of drugs targeting the bacterial processivity factor of Gram-negative bacteria as a promising new class of antibiotics., Bifunctional peptides targeting both the translation and the replication machineries have been developed and shown to act as new antimicrobials.
Published: 2020
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2. Bioactive micropatterning of biomaterials for induction of endothelial progenitor cell differentiation: Acceleration of in situ endothelialization

Author: Gaétan Laroche, Pascale Chevallier, Andrée-Anne Guay-Bégin, Marie-Christine Durrieu, Caroline Royer, Laurence Bordenave, Christel Chanseau, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Département de Génie des Mines, de la Métallurgie et des Matériaux [Quebec, Canada], Université Laval [Québec] (ULaval), CHU de Québec–Université Laval, Centre de Recherche sur les Matériaux Avancés [Quebec, Canada] (CERMA), Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chassande, Olivier, and Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: In situ, Materials science, Surface Properties, [SDV]Life Sciences [q-bio], 0206 medical engineering, Cell, Biomedical Engineering, in situ differentiation, Biocompatible Materials, 02 engineering and technology, Endothelial progenitor cell, endothelialization, Biomaterials, Cell Adhesion, medicine, Humans, Progenitor cell, Cells, Cultured, surface functionalization, endothelial progenitor cells, peptides grafting, Lineage markers, Sitagliptin Phosphate, Metals and Alloys, Cell Differentiation, Adhesion, 021001 nanoscience & nanotechnology, 020601 biomedical engineering, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, cardiovascular system, Ceramics and Composites, Surface modification, 0210 nano-technology, Oligopeptides, Micropatterning
Abstract: International audience; Synthetic grafts do not provide an appealing surface for endothelial cells to adhere and colonize the inner surface. To promote in situ endothelialization the following aspect has to be taken into account, endothelial progenitor cells (EPCs) needs to be mobilized on the surface of the graft. The surface of the graft has to be sufficiently biocompatible to create a prone environment for the EPCs to adhere, proliferate and, differentiate to form a layer and subsequently improve graft patency. In this work, two active molecules GRGDS and sitagliptin, were chosen for their abilities to recruit, enhance adhesion and induce differentiation of endothelial progenitor cells. They were grafted on PET surfaces in order to provide restrained cues triggering cell alignment and evaluate the influence of such structuration on EPCs fate. We then analyze cell behavior onto functionalized biomaterials. Their abilities to control EPCs fate were demonstrated via RT-qPCR, immunofluorescence, and enzymatic tests. The GRGDS/sitagliptin 100 × 10 surface enables to reduce the stemness phenotype on EPCs and induce the expression of endothelial lineage markers. These results highlight the importance of spatial patterning cues in guiding EPCs organization and function, which may have clinical relevance in the development of vascular grafts that promote patency.
Published: 2020
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3. Structural features of the interaction of MapZ with FtsZ and membranes in Streptococcus pneumoniae

Author: Denis Martinez, Jean-Pierre Simorre, Catherine M. Bougault, Birgit Habenstein, Jean-Pierre Lavergne, Isabel Ayala, Daphna Fenel, Marine Restelli, Christophe Grangeasse, Tomas Hosek, Cécile Morlot, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), iR-RMN-THC Fr3050 CNRS, ISBG, UMS 3518 CNRS-CEA-UGA-EMBL, Plateforme RMN, Microscopie électronique, ANR-15-CE32-0001,Map-CellDiv,MapZ: caractérisation d'un nouveau mécanisme de régulation de la division cellulaire bactérienne(2015), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), ANR-10-INBS-0005-02,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), and École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cell division, 030106 microbiology, lcsh:Medicine, Article, Cell membrane, 03 medical and health sciences, NMR spectroscopy, Bacterial Proteins, Bacterial development, Extracellular, medicine, Electron microscopy, FtsZ, lcsh:Science, Bacterial structural biology, Multidisciplinary, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Cell Membrane, lcsh:R, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Transmembrane domain, Cytoskeletal Proteins, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Membrane, medicine.anatomical_structure, Streptococcus pneumoniae, Structural biology, Cytoplasm, Biophysics, biology.protein, lcsh:Q, Pathogens
Abstract: MapZ localizes at midcell and acts as a molecular beacon for the positioning of the cell division machinery in the bacterium Streptococcus pneumoniae. MapZ contains a single transmembrane helix that separates the C-terminal extracellular domain from the N-terminal cytoplasmic domain. Only the structure and function of the extracellular domain is known. Here, we demonstrate that large parts of the cytoplasmic domain is intrinsically disordered and that there are two regions (from residues 45 to 68 and 79 to 95) with a tendency to fold into amphipathic helices. We further reveal that these regions interact with the surface of liposomes that mimic the Streptococcus pneumoniae cell membrane. The highly conserved and unfolded N-terminal region (from residues 17 to 43) specifically interacts with FtsZ independently of FtsZ polymerization state. Moreover, we show that MapZ phosphorylation at positions Thr67 and Thr68 does not impact the interaction with FtsZ or liposomes. Altogether, we propose a model in which the MapZ-mediated recruitment of FtsZ to mid-cell is modulated through competition of MapZ binding to the cell membrane. The molecular interplay between the components of this tripartite complex could represent a key step toward the complete assembly of the divisome.
Published: 2020
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4. Design, synthesis, and biological evaluation of a multifunctional neuropeptide-Y conjugate for selective nuclear delivery of radiolanthanides

Author: Chastel, Adrien, Worm, Dennis, Alves, Isabel, Vimont, Delphine, Petrel, Melina, Fernandez, Samantha, Garrigue, Philippe, Fernandez, Philippe, Hindié, Elif, Beck-Sickinger, Annette, Morgat, Clément, Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [Leipzig], Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Bordeaux Imaging Center (BIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut François Magendie-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig, Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Sub-cellular delivery, lcsh:Medical physics. Medical radiology. Nuclear medicine, Breast cancer, [SDV]Life Sciences [q-bio], lcsh:R895-920, 161Tb, Neuropeptide-Y, Auger-emitter, Tb-161, Original Research
Abstract: International audience; Background Targeting G protein-coupled receptors on the surface of cancer cells with peptide ligands is a promising concept for the selective tumor delivery of therapeutically active cargos, including radiometals for targeted radionuclide therapy (TRT). Recently, the radiolanthanide terbium-161 (Tb-161) gained significant interest for TRT application, since it decays with medium-energy beta-radiation but also emits a significant amount of conversion and Auger electrons with short tissue penetration range. The therapeutic efficiency of radiometals emitting Auger electrons, like Tb-161, can therefore be highly boosted by an additional subcellular delivery into the nucleus, in order to facilitate maximum dose deposition to the DNA. In this study, we describe the design of a multifunctional, radiolabeled neuropeptide-Y (NPY) conjugate, to address radiolanthanides to the nucleus of cells naturally overexpressing the human Y-1 receptor (hY(1)R). By using solid-phase peptide synthesis, the hY(1)R-preferring [F-7,P-34]-NPY was modified with a fatty acid, a cathepsin B-cleavable linker, followed by a nuclear localization sequence (NLS), and a DOTA chelator (compound pb12). In this proof-of-concept study, labeling was performed with either native terbium-159 (Tb-nat), as surrogate for Tb-161, or with indium-111 (In-111). Results [Tb-nat]Tb-pb12 showed a preserved high binding affinity to endogenous hY(1)R on MCF-7 cells and was able to induce receptor activation and internalization similar to the hY(1)R-preferring [F-7,P-34]-NPY. Specific internalization of the In-111-labeled conjugate into MCF-7 cells was observed, and importantly, time-dependent nuclear uptake of In-111 was demonstrated. Study of metabolic stability showed that the peptide is insufficiently stable in human plasma. This was confirmed by injection of [In-111]In-pb12 in nude mice bearing MCF-7 xenograft which showed specific uptake only at very early time point. Conclusion The multifunctional NPY conjugate with a releasable DOTA-NLS unit represents a promising concept for enhanced TRT with Auger electron-emitting radiolanthanides. Our research is now focusing on improving the reported concept with respect to the poor plasmatic stability of this promising radiopeptide.
Published: 2020
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5. Weaving of bacterial cellulose by the Bcs secretion systems

Author: Axel Siroy, Petya V. Krasteva, Wiem Abidi, Lucía Torres-Sánchez, Institut Européen de Chimie et Biologie (IECB), Institut Européen de Chimie et de Biologie, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), European Project: 0757507(2008), KRASTEVA, Petya Violinova, Combinatorial Set Theory - 2008-06-01 - 2013-05-31 - 0757507 - VALID, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), and École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio], synthase-dependent systems, Extracellular matrix component, Cooperativity, Biology, Polysaccharide, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, Polysaccharides, bacterial cellulose secretion (Bcs), Secretion, Cellulose, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Bacteria, 030302 biochemistry & molecular biology, Biofilm, matrix exopolysaccharides, [SDV] Life Sciences [q-bio], Infectious Diseases, c-di-GMP signaling, chemistry, Biochemistry, Bacterial cellulose, Biofilms, Biosynthetic process, biofilm formation
Abstract: Cellulose is the most abundant biological compound on Earth and while it is the predominant building constituent of plants, it is also a key extracellular matrix component in many diverse bacterial species. While bacterial cellulose was first described in the 19th century, it was not until this last decade that a string of structural works provided insights into how the cellulose synthase BcsA, assisted by its inner-membrane partner BcsB, senses c-di-GMP to simultaneously polymerize its substrate and extrude the nascent polysaccharide across the inner bacterial membrane. It is now established that bacterial cellulose can be produced by several distinct types of cellulose secretion systems and that in addition to BcsAB, they can feature multiple accessory subunits, often indispensable for polysaccharide production. Importantly, the last years mark significant progress in our understanding not only of cellulose polymerization per se but also of the bigger picture of bacterial signaling, secretion system assembly, biofilm formation and host tissue colonization, as well as of structural and functional parallels of this dominant biosynthetic process between the bacterial and eukaryotic domains of life. Here, we review current mechanistic knowledge on bacterial cellulose secretion with focus on the structure, assembly and cooperativity of Bcs secretion system components.
Published: 2021
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6. Mass spectrometry imaging of mice brain lipid profile changes over time under high fat diet

Author: Boutayna Rhourri-Frih, Daniela Cota, Gianluca Sighinolfi, Landry Blanc, Samantha Clark, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, ANR-10-LABX-0043,BRAIN,Bordeaux Region Aquitaine Initiative for Neuroscience(2010), ANR-13-BSV4-0006,NeuroNutriSens,Dissection des mécanismes hypothalamiques impliqués dans la détection du statut nutritionnel et régulation de la prise alimentaire via les interactions entre mTORC1, les mélanocortines et les endocannabinoïdes.(2013), ANR-17-CE14-0007,BABrain,La signalisation des acides biliaires dans le cerveau et son rôle dans le contrôle métabolique(2017), ANR-18-CE14-0029,MitObesity,Rôle du récepteur aux cannabinoïdes de type 1 mitochondriale dans les circuits hypothalamiques et son interaction avec la voie mTORC1 dans l'obésité.(2018), ANR-10-EQPX-0008,OPTOPATH,Innovations instrumentales et procédurales en psychopathologie expérimentale chez le rongeur(2010), Admin, Oskar, Bordeaux Region Aquitaine Initiative for Neuroscience - - BRAIN2010 - ANR-10-LABX-0043 - LABX - VALID, Blanc 2013 - Dissection des mécanismes hypothalamiques impliqués dans la détection du statut nutritionnel et régulation de la prise alimentaire via les interactions entre mTORC1, les mélanocortines et les endocannabinoïdes. - - NeuroNutriSens2013 - ANR-13-BSV4-0006 - Blanc 2013 - VALID, La signalisation des acides biliaires dans le cerveau et son rôle dans le contrôle métabolique - - BABrain2017 - ANR-17-CE14-0007 - AAPG2017 - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Rôle du récepteur aux cannabinoïdes de type 1 mitochondriale dans les circuits hypothalamiques et son interaction avec la voie mTORC1 dans l'obésité. - - MitObesity2018 - ANR-18-CE14-0029 - AAPG2018 - VALID, Innovations instrumentales et procédurales en psychopathologie expérimentale chez le rongeur - - OPTOPATH2010 - ANR-10-EQPX-0008 - EQPX - VALID, Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), and Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Data Analysis, medicine.medical_specialty, Calorie, Time Factors, Science, Overweight, Diet, High-Fat, 01 natural sciences, Article, Mass Spectrometry, 03 medical and health sciences, Mice, Weight loss, Tandem Mass Spectrometry, Internal medicine, Lipidomics, medicine, Image Processing, Computer-Assisted, Animals, Metabolomics, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, 2. Zero hunger, Cerebral atrophy, 0303 health sciences, Multidisciplinary, medicine.diagnostic_test, Chemistry, 010401 analytical chemistry, Body Weight, Brain, Lipidome, medicine.disease, Lipid Metabolism, Obesity, Chemical biology, Lipids, 0104 chemical sciences, Endocrinology, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Lipid profile, Biomarkers, Chromatography, Liquid
Abstract: Overweight and obesity have been shown to significantly affect brain structures and size. Obesity has been associated with cerebral atrophy, alteration of brain functions, including cognitive impairement, and psychiatric diseases such as depression. Given the importance of lipids in the structure of the brain, here, by using 47 mice fed a high fat diet (HFD) with 60% calories from fat (40% saturated fatty acids) and 20% calories from carbohydrates and age-matched control animals on a normal chow diet, we examined the effects of HFD and diet-induced obesity on the brain lipidome. Using a targeted liquid chromatography mass spectrometry analysis and a non-targeted mass spectrometry MALDI imaging approach, we show that the relative concentration of most lipids, in particular brain phospholipids, is modified by diet-induced obesity (+ 40%of body weight). Use of a non-targeted MALDI-MS imaging approach further allowed define cerebral regions of interest (ROI) involved in eating behavior and changes in their lipid profile. Principal component analysis (PCA) of the obese/chow lipidome revealed persistence of some of the changes in the brain lipidome of obese animals even after their switch to chow feeding and associated weight loss. Altogether, these data reveal that HFD feeding rapidly modifies the murine brain lipidome. Some of these HFD-induced changes persist even after weight loss, implying that some brain sequelae caused by diet-induced obesity are irreversible.
Published: 2021
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7. Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts

Author: Sisareuth Tan, Jean-Sébastien Silvestre, Kamaleswaran Keirththana, Alain Brisson, Thi Anh-Dao Tran, José Vilar, Philippe Menasché, Paul Alayrac, Thomas Hamada, Maria Franca Perotto, Nadia El Harane, Reem Al-Daccak, Dominique Charron, Laetitia Pidial, Valérie Bellamy, Nisa Renault, Hocine Rachid Hocine, Chloé Guillas, Manon Desgres, Ingrid Gomez, Bruna Lima Correa, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Curie [Paris], Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Fujifilm Cellular Dynamics Inc [Madison, WI, USA], Service de Chirurgie Cardiovasculaire [Hôpital Européen Georges Pompidou - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), LIMA CORREA, Bruna, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Male, 0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Neutrophils, Physiology, T cell, Lymphocyte, Induced Pluripotent Stem Cells, Myocardial Infarction, 030204 cardiovascular system & hematology, Monocytes, Cell Line, Extracellular Vesicles, 03 medical and health sciences, Paracrine signalling, 0302 clinical medicine, Immune system, Interferon, Physiology (medical), medicine, Animals, Humans, Regeneration, Myocytes, Cardiac, Progenitor cell, Cell Proliferation, Heart Failure, Chemistry, Macrophages, Myocardium, NKG2D, Coculture Techniques, Rats, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, Phenotype, 030104 developmental biology, medicine.anatomical_structure, Immunology, Cytokines, Inflammation Mediators, Cardiology and Cardiovascular Medicine, CD80, medicine.drug
Abstract: AimsThe cardioprotective effects of human induced pluripotent stem cell-derived cardiovascular progenitor cells (CPC) are largely mediated by the paracrine release of extracellular vesicles (EV). We aimed to assess the immunological behaviour of EV-CPC, which is a prerequisite for their clinical translation.Methods and resultsFlow cytometry demonstrated that EV-CPC expressed very low levels of immune relevant molecules including HLA Class I, CD80, CD274 (PD-L1), and CD275 (ICOS-L); and moderate levels of ligands of the natural killer (NK) cell activating receptor, NKG2D. In mixed lymphocyte reactions, EV-CPC neither induced nor modulated adaptive allogeneic T cell immune responses. They also failed to induce NK cell degranulation, even at high concentrations. These in vitro effects were confirmed in vivo as repeated injections of EV-CPC did not stimulate production of immunoglobulins or affect the interferon (IFN)-γ responses from primed splenocytes. In a mouse model of chronic heart failure, intra-myocardial injections of EV-CPC, 3 weeks after myocardial infarction, decreased both the number of cardiac pro-inflammatory Ly6Chigh monocytes and circulating levels of pro-inflammatory cytokines (IL-1α, TNF-α, and IFN-γ). In a model of acute infarction, direct cardiac injection of EV-CPC 2 days after infarction reduced pro-inflammatory macrophages, Ly6Chigh monocytes, and neutrophils in heart tissue as compared to controls. EV-CPC also reduced levels of pro-inflammatory cytokines IL-1α, IL-2, and IL-6, and increased levels of the anti-inflammatory cytokine IL-10. These effects on human macrophages and monocytes were reproduced in vitro; EV-CPC reduced the number of pro-inflammatory monocytes and M1 macrophages, while increasing the number of anti-inflammatory M2 macrophages.ConclusionsEV-CPC do not trigger an immune response either in in vitro human allogeneic models or in immunocompetent animal models. The capacity for orienting the response of monocyte/macrophages towards resolution of inflammation strengthens the clinical attractiveness of EV-CPC as an acellular therapy for cardiac repair.
Published: 2020
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8. The glutamate receptor GluK2 contributes to the regulation of glucose homeostasis and its deterioration during aging

Author: Abarkan, Myriam, GAITAN, Julien, Lebreton, Fanny, Perrier, Romain, Jaffredo, Manon, Mulle, Christophe, Magnan, Christophe, Raoux, Matthieu, Lang, Jochen, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Pôle de recherche pour l'organisation et la diffusion de l'information géographique (PRODIG), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Sorbonne (UP4)-École pratique des hautes études (EPHE)-Institut de Recherche pour le Développement (IRD)-Université Panthéon-Sorbonne (UP1), Indisciplinary Institute for Neuroscience, UMR 5297, Mulle, Christophe, Transistors multimodaux sensibles aux ions à polymères ambivalents pour biocapteurs hybrides - - MULTISPOT2017 - ANR-17-CE09-0015 - AAPG2017 - VALID, Identification de biomarqueurs du stress et de l'inflammation des cellules B pancréatiques en explorant les communications inter-organes dans des modèles précliniques d'obésité et de diabète de type 2 - - betadiamark2015 - ANR-15-CE14-0027 - AAPG2015 - VALID, Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Interdisciplinary Institute for Neuroscience [Bordeaux] (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MA and FL hold PhD scholarships from the French Research Agency (ANR-17-CE09-0015 MULTISPOT to JL) or the French Ministry of Education (to JL).We acknowledge institution a lfunding from the CNRS and the University of Bordeaux (JL). C Magnan received funding from the French Research Agency (ANR PRCI-15-CE14-0027-01 Beta Dia-mark) and the French Society for Study of Diabetes (SFD-MSD)., ANR-17-CE09-0015,MULTISPOT,Transistors multimodaux sensibles aux ions à polymères ambivalents pour biocapteurs hybrides(2017), ANR-15-CE14-0027,betadiamark,Identification de biomarqueurs du stress et de l'inflammation des cellules B pancréatiques en explorant les communications inter-organes dans des modèles précliniques d'obésité et de diabète de type 2(2015), and École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Blood Glucose, Male, endocrine system, Aging, lcsh:Internal medicine, Insulin/metabolism, GluK2, kainate receptor subunit GluK2, OGTT, oral glucose tolerance test, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Brief Communication, MEA, microelectrode array, Islets of Langerhans, Mice, Insulin-Secreting Cells/metabolism, PyrCT, pyruvate challenge test, Receptors, Kainic Acid, Insulin-Secreting Cells, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Insulin Secretion, Receptors, Glucagon, Insulin, Animals, Glucose/metabolism, Homeostasis, Receptors, Glucagon/metabolism, Glucagon/metabolism, lcsh:RC31-1245, ComputingMilieux_MISCELLANEOUS, Glucagon-Secreting Cells/metabolism, Microelectrode array, ITT, insulin tolerance test, Mice, Knockout, GRIK2, Blood Glucose/metabolism, GluK2, [CHIM.MATE]Chemical Sciences/Material chemistry, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Glucagon, Kainate receptor, Mice, Inbred C57BL, Glucose, Receptors, Kainic Acid/metabolism, Glucagon-Secreting Cells, IPGTT, intraperitoneal glucose tolerance test, Female, Insulin Resistance, Islets of Langerhans/metabolism, Islets
Abstract: Objective Islets secrete neurotransmitters including glutamate which participate in fine regulation of islet function. The excitatory ionotropic glutamate receptor GluK2 of the kainate receptor family is widely expressed in brain and also found in islets, mainly in α and γ cells. α cells co-release glucagon and glutamate and the latter increases glucagon release via ionotropic glutamate receptors. However, neither the precise nature of the ionotropic glutamate receptor involved nor its role in glucose homeostasis is known. As isoform specific pharmacology is not available, we investigated this question in constitutive GluK2 knock-out mice (GluK2−/−) using adult and middle-aged animals to also gain insight in a potential role during aging. Methods We compared wild-type GluK2+/+ and knock-out GluK2−/− mice using adult (14–20 weeks) and middle-aged animals (40–52 weeks). Glucose (oral OGTT and intraperitoneal IPGTT) and insulin tolerance as well as pyruvate challenge tests were performed according to standard procedures. Parasympathetic activity, which stimulates hormones secretion, was measured by electrophysiology in vivo. Isolated islets were used in vitro to determine islet β-cell electrical activity on multi-electrode arrays and dynamic secretion of insulin as well as glucagon was determined by ELISA. Results Adult GluK2−/− mice exhibit an improved glucose tolerance (OGTT and IPGTT), and this was also apparent in middle-aged mice, whereas the outcome of pyruvate challenge was slightly improved only in middle-aged GluK2−/− mice. Similarly, insulin sensitivity was markedly enhanced in middle-aged GluK2−/− animals. Basal and glucose-induced insulin secretion in vivo was slightly lower in GluK2−/− mice, whereas fasting glucagonemia was strongly reduced. In vivo recordings of parasympathetic activity showed an increase in basal activity in GluK2−/− mice which represents most likely an adaptive mechanism to counteract hypoglucagonemia rather than altered neuronal mechanism. In vitro recording demonstrated an improvement of glucose-induced electrical activity of β-cells in islets obtained from GluK2−/− mice at both ages. Finally, glucose-induced insulin secretion in vitro was increased in GluK2−/− islets, whereas glucagon secretion at 2 mmol/l of glucose was considerably reduced. Conclusions These observations indicate a general role for kainate receptors in glucose homeostasis and specifically suggest a negative effect of GluK2 on glucose homeostasis and preservation of islet function during aging. Our observations raise the possibility that blockade of GluK2 may provide benefits in glucose homeostasis especially during aging., Highlights • KO of GluK2 improved glucose tolerance and lowered fasting glucagon levels in vivo. • KO of GluK2 reduced in vitro islet glucagon secretion and increased β-cell activity. • GluK2 contributes to the known impact of aging on glucose homeostasis.
Published: 2019
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9. Crystal structures capture multiple stoichiometric states of an aqueous self-assembling oligourea foldamer

Author: Cameron D. Mackereth, Gavin W. Collie, Sung Hyun Yoo, Frédéric Rosu, Caterina Lombardo, Valérie Gabelica, Gilles Guichard, Karolina Pulka-Ziach, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), AstraZeneca [Cambridge, UK], Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculty of Chemistry [Warsaw], University of Warsaw (UW), Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie (IECB), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), and Admin, Oskar
Subjects: Models, Molecular, Crystal structure, 010402 general chemistry, Crystallography, X-Ray, 01 natural sciences, Catalysis, Self assembling, Materials Chemistry, Urea, Aqueous solution, Molecular Structure, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Chemistry, Metals and Alloys, Foldamer, Water, Stereoisomerism, General Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Crystallography, Polymorphism (materials science), Helix, Ceramics and Composites, Stoichiometry
Abstract: We report here an oligourea foldamer able to self-assemble in aqueous conditions into helix bundles of multiple stoichiometries. Importantly, we report crystal structures of several of these stoichiometries, providing a series of high-resolutions snap-shots of the structural polymorphism of this foldamer and uncovering a novel self-assembly.
Published: 2021
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10. Bacteria associated with wood tissues of Esca‐diseased grapevines: functional diversity and synergy with Fomitiporia mediterranea to degrade wood components

Author: Patrice Rey, Rana Haidar, Brice Kauffmann, Stéphane Compant, Eléonore Attard, Jessica Vallance, Antoine Loquet, Ahmad Saad, Amira Yacoub, Birgit Habenstein, Rémy Guyoneaud, Livio Antonielli, Axelle Grélard, Santé et agroécologie du vignoble (UMR SAVE), Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Tishreen University (Mechatronic Department), Austrian Institute of Technology [Vienna] (AIT), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Soutien à la Recherche de l'Institut Européen de Chimie Biologique, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Européen de Chimie et de Biologie-Université Sciences et Technologies - Bordeaux 1-Institut de Chimie du CNRS (INC), Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Tishreen University, Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and DESAILLY, Marion
Subjects: [SDE] Environmental Sciences, Vitis vinifera L grapevine, Fomitiporia mediterranea, Fungus, Microbiology, Endophyte, complex mixtures, 03 medical and health sciences, Paenibacillus, chemistry.chemical_compound, Botany, Humans, Vitis, Cellulose, Ecology, Evolution, Behavior and Systematics, Plant Diseases, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Bacteria, biology, 030306 microbiology, biology.plant_disease_cause, Basidiomycota, Xanthomonadaceae, technology, industry, and agriculture, 15. Life on land, biology.organism_classification, Wood, Basidiomycete fungi, chemistry, [SDE]Environmental Sciences, Pseudomonadaceae
Abstract: International audience; Fungi are considered to cause grapevine trunk diseases such as esca that result in wood degradation. For instance, the basidiomycete Fomitiporia mediterranea (Fmed) is overabundant in white rot, a key type of wood-necrosis associated with esca. However, many bacteria colonize the grapevine wood too, including the white rot. In this study, we hypothesized that bacteria colonizing grapevine wood interact, possibly synergistically, with Fmed and enhance the fungal ability to degrade wood. We isolated 237 bacterial strains from esca-affected grapevine wood. Most of them belonged to the families Xanthomonadaceae and Pseudomonadaceae. Some bacterial strains that degrade grapevine-wood components such as cellulose and hemicellulose did not inhibit Fmed growth in vitro. We proved that the fungal ability to degrade wood can be strongly influenced by bacteria inhabiting the wood. This was shown with a cellulolytic and xylanolytic strain of the Paenibacillus genus, which displays synergistic interaction with Fmed by enhancing the degradation of wood structures. Genome analysis of this Paenibacillus strain revealed several gene clusters such as those involved in the expression of carbohydrate-active enzymes, xylose utilization and vitamin metabolism. In addition, certain other genetic characteristics of the strain allow it to thrive as an endophyte in grapevine and influence the wood degradation by Fmed. This suggests that there might exist a synergistic interaction between the fungus Fmed and the bacterial strain mentioned above, enhancing grapevine wood degradation. Further step would be to point out its occurrence in mature grapevines to promote esca disease development.
Published: 2021
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11. Single-molecule mechanics of synthetic aromatic amide helices: Ultrafast and robust non-dissipative winding

Author: Xuesong Li, Victor Maurizot, Anne-Sophie Duwez, Francesco Zerbetto, Ivan Huc, Floriane Devaux, Evangelos Bakalis, Damien Sluysmans, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), European Project: 320892,EC:FP7:ERC,ERC-2012-ADG_20120216,A2F2(2013), European Project: IDS-FunMat, École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Devaux F., Li X., Sluysmans D., Maurizot V., Bakalis E., Zerbetto F., Huc I., and Duwez A.-S.
Subjects: Materials science, General Chemical Engineering, 02 engineering and technology, helical folding, 010402 general chemistry, 01 natural sciences, Biochemistry, SDG9: Industry, innovation, and infrastructure, molecular machines with tailored propertie, reversible processes, foldamer, Materials Chemistry, Environmental Chemistry, Molecule, foldamers, Elasticity (economics), Mechanical energy, AFM force spectroscopy, single-molecule mechanics, Biochemistry (medical), Force spectroscopy, molecular machines with tailored properties, General Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, reversible processe, 0104 chemical sciences, Folding (chemistry), Chemical physics, Dissipative system, Protein folding, elasticity, 0210 nano-technology, Ultrashort pulse
Abstract: Summary Because of proteins’ many degrees of conformational freedom, programming protein folding dynamics, overall elasticity, and motor functions remains an elusive objective. Instead, smaller and simpler objects, such as synthetic foldamers, may be amenable to design. However, little is known about their mechanical performance. Here, we show that reducing molecular size may not compromise mechanical properties. We report that helical aromatic oligoamides as small as 1 nm possess outstanding elasticity and outperform most natural helices. Using single-molecule force spectroscopy, we characterize their folding trajectories and intermediate states. We show that they cooperatively and reversibly unwind at high forces. They extend up to 3.8 times their original length and rewind against considerable forces on a timescale of 10 μs. Pulling and relaxing cycles follow the same trace up to a very high loading rate, indicating that the mechanical energy accumulated during the stretching does not dissipate and is immediately reusable.
Published: 2021
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12. A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses

Author: Meunier, Thomas, Desmarets, Lowiese, Bordage, Simon, Bamba, Moussa, Hervouet, Kévin, Rouillé, Yves, François, Nathan, Decossas, Marion, Sencio, Valentin, Trottein, François, Honora Tra Bi, Fézan, Lambert, Olivier, Dubuisson, Jean, Belouzard, Sandrine, Sahpaz, Sevser, Séron, Karin, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), CHU Lille, Université de Liège, JUNIA (JUNIA), Université Nangui Abrogoua, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Polytechnique de Bordeaux (Bordeaux INP), Séron, Karin, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université catholique de Lille (UCL), Université Nangui Abrogoua (UNA), and Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Biological Products, SARS-CoV-2, viruses, [SDV]Life Sciences [q-bio], Cryoelectron Microscopy, COVID-19, virus diseases, respiratory system, Antiviral Agents, respiratory tract diseases, [SDV] Life Sciences [q-bio], parasitic diseases, Middle East Respiratory Syndrome Coronavirus, Humans
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against human CoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and Middle East respiratory syndrome coronavirus (MERS-CoV), and its mechanism of action was further assessed, showing that Pba is an inhibitor of coronavirus entry by directly targeting the viral particle. Interestingly, the antiviral activity of Pba depends on light exposure, and Pba was shown to inhibit virus-cell fusion by stiffening the viral membrane, as demonstrated by cryoelectron microscopy. Moreover, Pba was shown to be broadly active against several other enveloped viruses and reduced SARS-CoV-2 and MERS-CoV replication in primary human bronchial epithelial cells. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity that holds potential for COVID-19 therapy or disinfection of SARS-CoV-2-contaminated surfaces.
Published: 2021
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13. Structural and molecular basis of cross-seeding barriers in amyloids

Author: Denis Martinez, Abdelmajid Noubhani, Loren B. Andreas, Guido Pintacuda, Benjamin Bardiaux, Brice Kauffmann, Asen Daskalov, Mélanie Berbon, Antoine Loquet, Joseph S. Wall, Virginie Coustou, Nadia El Mammeri, Jan Stanek, Sven J. Saupe, Birgit Habenstein, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre de Résonance Magnetique Nucleaire (CRMN), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Brookhaven National Laboratory [Upton, NY] (BNL), UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY)-U.S. Department of Energy [Washington] (DOE), We acknowledge financial support from the European Research Council (ERC) under the European Unions Horizon 2020 Research and Innovation Programme (ERC-2015-CoG GA 648974 to G.P. and ERC-2015-StG GA 639020 to A.L.), IdEx Bordeaux (Chaire d’Installation to B.H., ANR-10-IDEX-03-02), the Agence Nationale de la Recherche (ANR) (ANR-14-CE09-0020-01 to A.L., ANR-13-PDOC-0017-01 to B.H. and ANR-17-CE11-0035 to S.J.S), the INCEPTION project (Programme d'investissements d'avenir/ANR-16-CONV-0005) and the CNRS (IR-RMN FR3050). J.S. and L.B.A. were supported by individual Marie Sklodowska-Curie incoming fellowships (grant agreements 661799 'COMPLEX-FAST-MAS' and 624918 'MEM-MAS'). A.D. was supported by the Nouvelle Aquitaine Regional Council., We thank the Nouvelle Aquitaine Regional Council, University of Bordeaux, and the Contrat Plan Etat-Region (CPER) CampusB Bordeaux for the acquisition of the NMR equipment. This work has benefited from the Biophysical and Structural Chemistry Platform at IECB, CNRS UMS 3033, INSERM US001., ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), ANR-14-CE09-0020,NanoSSNMR,Nanostructures biologiques et synthétiques étudiées par Résonance Magnétique Nucléaire du Solide(2014), ANR-13-PDOC-0017,SUPRAMOL,Structures d'Assemblages Supramoléculaires par RMN du Solide : le Pseudopilus du Système de Sécrétion de Type II et le Tube de Queue du Bactériophage(2013), ANR-17-CE11-0035,SFAS,Structure et fonctions de motifs amyloïdes impliqués dans la transduction du signal(2017), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 648974,H2020,ERC-2014-CoG,P-MEM-NMR(2015), European Project: 639020,H2020,ERC-2014-STG,Weakinteract(2015), European Project: 661799,H2020,H2020-MSCA-IF-2014,COMPLEX-fastMAS-NMR(2016), European Project: 624918,EC:FP7:PEOPLE,FP7-PEOPLE-2013-IIF,MEM-MAS(2014), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), U.S. Department of Energy [Washington] (DOE)-UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), and State University of New York (SUNY)-State University of New York (SUNY)
Subjects: 0301 basic medicine, Protein Folding, Amyloid, Prions, Prion strain, Model system, Amyloidogenic Proteins, Computational biology, Biology, 010402 general chemistry, 01 natural sciences, Models, Biological, Podospora anserina, Fungal Proteins, prion, 03 medical and health sciences, Protein Aggregates, 0302 clinical medicine, Podospora, Amino Acid Sequence, Prion protein, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Conserved Sequence, 030304 developmental biology, cross-seeding, 0303 health sciences, Multidisciplinary, food and beverages, amyloid, Biological Sciences, biology.organism_classification, Sequence identity, 0104 chemical sciences, Protein Structure, Tertiary, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Strain specificity, nuclear magnetic resonance, 030104 developmental biology, sequence to fold, Sequence Alignment, 030217 neurology & neurosurgery
Abstract: Neurodegenerative disorders are frequently associated with β-sheet-rich amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behaviour and distinct patho-phenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prion protein from the fungus Podospora anserina represents a model system to study the fundamental properties of prion amyloids. Here, we report the amyloid prion structure of HELLF, a distant homolog of the model prion HET-s. We find that these two amyloids, sharing only 17% sequence identity, have nearly identical β-solenoid folds but lack cross-seeding ability in vivo, indicating that prion specificity can differ in extremely similar amyloid folds. We engineer the HELLF sequence to explore the limits of the sequence-to-fold conservation and to pinpoint determinants of cross-seeding and prion specificity. We find that amyloid fold conservation occurs even at an exceedingly low level of identity to HET-s (5%). Next, we derive a HELLF-based sequence, termed HEC, able to breach the cross-seeding barrier in vivo between HELLF and HET-s, unveiling determinants controlling cross-seeding at residue level. These findings show that virtually identical amyloid backbone structures might not be sufficient for cross-seeding and that critical side-chain positions could determine the seeding specificity of an amyloid fold. Our work redefines the conceptual boundaries of prion strain and shed new light on key molecular features concerning an important class of pathogenic agents.
Published: 2021
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14. Revealing the elasticity of an individual aortic fiber during ageing at nanoscale by in situ atomic force microscopy †

Author: Laurent Martiny, Sébastien Blaise, Alexandre Berquand, Laëtitia Gorisse, Philippe Gillery, Laurent Duca, Béatrice Romier-Crouzet, Pascal Maurice, Christine Pietrement, Fatouma Touré, Hervé Sartelet, Michael Molinari, Stéphane Jaisson, Aubéri Henry, Amar Bennasroune, Amandine Wahart, Laboratoire de Recherche en Nanosciences - EA 4682 (LRN), SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and MAURICE, Pascal
Subjects: Fluorescence-lifetime imaging microscopy, Aging, Materials science, 030204 cardiovascular system & hematology, Pulse Wave Analysis, Microscopy, Atomic Force, Extracellular matrix, 03 medical and health sciences, Mice, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.artery, medicine, Animals, General Materials Science, Elasticity (economics), [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], Pulse wave velocity, Aorta, 030304 developmental biology, 0303 health sciences, biology, [PHYS.MECA.BIOM] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], Stiffness, Elasticity, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Ageing, biology.protein, medicine.symptom, Elastin, Biomedical engineering
Abstract: International audience; Arterial stiffness is a complex process affecting the aortic tree that significantly contributes to cardiovascular diseases (systolic hypertension, coronary artery disease, heart failure or stroke). This process involves a large extracellular matrix remodeling mainly associated with elastin content decrease and collagen content increase. Additionally, various chemical modifications that accumulate with ageing have been shown to affect long-lived assemblies, such as elastic fibers, that could affect their elasticity. To precisely characterize the fiber changes and the evolution of its elasticity with ageing, high resolution and multimodal techniques are needed for precise insight into the behavior of a single fiber and its surrounding medium. In this study, the latest developments in atomic force microscopy and the related nanomechanical modes are used to investigate the evolution and in a near-physiological environment, the morphology and elasticity of aorta cross sections obtained from mice of different ages with an unprecedented resolution. In correlation with more classical approaches such as pulse wave velocity and fluorescence imaging, we demonstrate that the relative Young's moduli of elastic fibers, as well as those of the surrounding areas, significantly increase with ageing. This nanoscale characterization presents a new view on the stiffness process, showing that, besides the elastin and collagen content changes, elasticity is impaired at the molecular level, allowing a deeper understanding of the ageing process. Such nanomechanical AFM measurements of mouse tissue could easily be applied to studies of diseases in which elastic fibers suffer pathologies such as atherosclerosis and diabetes, where the precise quantification of fiber elasticity could better follow the fiber remodeling and predict plaque rupture. † Electronic supplementary information (ESI) available. See
Published: 2021
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15. Neural stem cells traffic functional mitochondria via extracellular vesicles

Author: Erika Fernandez-Vizarra, Carlo Viscomi, Ágnes Kittel, Sisareuth Tan, Christian Frezza, Stefano Pluchino, Cristiane Benincá, Nunzio Vicario, Massimo Zeviani, Tommaso Leonardi, Ben Peacock, Paul J. Lehner, Alice Braga, Joshua D. Bernstock, Aletta Van Den Bosch, Jayden A. Smith, Karin H. Muller, Carlos Bastos, Edit I. Buzás, Luca Peruzzotti-Jametti, Giulia Manferrari, Cory M. Willis, Alain Brisson, Nunzio Iraci, Rebecca Rogall, Nuno Faria, Grzegorz Krzak, James C Williamson, Nicholas J Matheson, Iacopo Bicci, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), European Project: 258803, Peruzzotti-Jametti, Luca [0000-0002-9396-5607], Bernstock, Joshua D [0000-0002-7814-3867], Willis, Cory M [0000-0001-7938-7276], Manferrari, Giulia [0000-0001-7062-1142], Rogall, Rebecca [0000-0003-0605-2322], Fernandez-Vizarra, Erika [0000-0002-2469-142X], Williamson, James C [0000-0002-2009-189X], Braga, Alice [0000-0003-3273-9742], van den Bosch, Aletta [0000-0001-8886-8928], Leonardi, Tommaso [0000-0002-4449-1863], Benincá, Cristiane [0000-0001-7933-860X], Vicario, Nunzio [0000-0001-5934-3962], Tan, Sisareuth [0000-0003-3633-6318], Bicci, Iacopo [0000-0001-6994-3857], Iraci, Nunzio [0000-0003-2146-9329], Smith, Jayden A [0000-0003-2307-8452], Peacock, Ben [0000-0002-7823-8719], Muller, Karin H [0000-0003-4693-8558], Brisson, Alain [0000-0003-0342-352X], Matheson, Nicholas J [0000-0002-3318-1851], Apollo - University of Cambridge Repository, Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bernstock, Joshua D. [0000-0002-7814-3867], Willis, Cory M. [0000-0001-7938-7276], Williamson, James C. [0000-0002-2009-189X], Smith, Jayden A. [0000-0003-2307-8452], Muller, Karin H. [0000-0003-4693-8558], and Matheson, Nicholas J. [0000-0002-3318-1851]
Subjects: 0301 basic medicine, Central Nervous System, Proteomics, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cell Membranes, Artificial Gene Amplification and Extension, Mitochondrion, Outer membrane proteins, Inbred C57BL, Exosomes, Biochemistry, Nervous System, Transgenic, White Blood Cells, Database and Informatics Methods, Mice, 0302 clinical medicine, Neural Stem Cells, Animal Cells, Medicine and Health Sciences, Computer software, Biology (General), Energy-Producing Organelles, Cells, Cultured, Phagocytes, Cultured, Proteomic Databases, General Neuroscience, Neural stem cell, Cell biology, Mitochondria, Polymerase chain reaction, medicine.anatomical_structure, Female, Stem cell, Cellular Structures and Organelles, Cellular Types, Anatomy, General Agricultural and Biological Sciences, Research Article, QH301-705.5, Cells, Immune Cells, Central nervous system, Immunology, Green Fluorescent Proteins, Mice, Transgenic, Biology, Bioenergetics, Research and Analysis Methods, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Extracellular Vesicles, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Organelle, medicine, Animals, Vesicles, Molecular Biology Techniques, Molecular Biology, Blood Cells, General Immunology and Microbiology, Biology and Life Sciences, Membrane Proteins, Biological Transport, Mesenchymal Stem Cells, Cell Biology, Microvesicles, Transplantation, Mice, Inbred C57BL, 030104 developmental biology, Biological Databases, 030217 neurology & neurosurgery
Abstract: Neural stem cell (NSC) transplantation induces recovery in animal models of central nervous system (CNS) diseases. Although the replacement of lost endogenous cells was originally proposed as the primary healing mechanism of NSC grafts, it is now clear that transplanted NSCs operate via multiple mechanisms, including the horizontal exchange of therapeutic cargoes to host cells via extracellular vesicles (EVs). EVs are membrane particles trafficking nucleic acids, proteins, metabolites and metabolic enzymes, lipids, and entire organelles. However, the function and the contribution of these cargoes to the broad therapeutic effects of NSCs are yet to be fully understood. Mitochondrial dysfunction is an established feature of several inflammatory and degenerative CNS disorders, most of which are potentially treatable with exogenous stem cell therapeutics. Herein, we investigated the hypothesis that NSCs release and traffic functional mitochondria via EVs to restore mitochondrial function in target cells. Untargeted proteomics revealed a significant enrichment of mitochondrial proteins spontaneously released by NSCs in EVs. Morphological and functional analyses confirmed the presence of ultrastructurally intact mitochondria within EVs with conserved membrane potential and respiration. We found that the transfer of these mitochondria from EVs to mtDNA-deficient L929 Rho0 cells rescued mitochondrial function and increased Rho0 cell survival. Furthermore, the incorporation of mitochondria from EVs into inflammatory mononuclear phagocytes restored normal mitochondrial dynamics and cellular metabolism and reduced the expression of pro-inflammatory markers in target cells. When transplanted in an animal model of multiple sclerosis, exogenous NSCs actively transferred mitochondria to mononuclear phagocytes and induced a significant amelioration of clinical deficits. Our data provide the first evidence that NSCs deliver functional mitochondria to target cells via EVs, paving the way for the development of novel (a)cellular approaches aimed at restoring mitochondrial dysfunction not only in multiple sclerosis, but also in degenerative neurological diseases., This study shows that neural stem cells are able to transfer functional mitochondria via extracellular vesicles to target cells both in vitro and in vivo, suggesting that functional mitochondrial transfer via extracellular vesicles is a signaling mechanism used by neural stem cells to modulate the physiology and metabolism of target cells.
Published: 2021
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16. β-Amyloid peptide interactions with biomimetic membranes: A multiparametric characterization

Author: Julien Cardin, Marc Since, Aurélie Malzert-Fréon, Christophe Cullin, Willy Smeralda, Sophie Corvaisier, Sophie Lecomte, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Nanomatériaux, Ions et Métamatériaux pour la Photonique (NIMPH), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), and École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Peptide, 02 engineering and technology, Biochemistry, Interactome, Fluorescence, Cell membrane, 03 medical and health sciences, chemistry.chemical_compound, Biomimetic Materials, Structural Biology, Phosphatidylcholine, Spectroscopy, Fourier Transform Infrared, medicine, Molecular Biology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Liposome, Amyloid beta-Peptides, Membranes, Chemistry, Membranes, Artificial, Biological membrane, General Medicine, Alzheimer's disease, Fluoresceins, 021001 nanoscience & nanotechnology, 3. Good health, Peptide Conformation, Kinetics, Membrane, medicine.anatomical_structure, Liposomes, Biophysics, 0210 nano-technology, β-Amyloid
Abstract: International audience; Alzheimer's disease is the most common form of senile dementia in the world, and amyloid β peptide1-42 (Aβ1-42) is one of its two principal biological hallmarks. While interactome concept was getting forward the scientific community, we proposed that the study of the molecular interactions of amyloid β peptide with the biological membranes will allow to highlight underlying mechanisms responsive of AD. We have developed two simple liposomal formulations (phosphatidylcholine, cholesterol, phosphatidylglycerol) mimicking neuronal cell membrane (composition, charge, curvature radius). Interactions with Aβ1-42 and mutant oG37C, a stable oligomeric form of the peptide, were characterized according to a simple multiparametric procedure based on ThT fluorescence, liposome leakage assay, ATR-FTIR spectroscopy. Kinetic aggregation, membrane damage and peptide conformation provided our first methodologic bases to develop an original model to describe interactions of Aβ peptide and lipids.
Published: 2021
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17. Structures of Pathological and Functional Amyloids and Prions, a Solid-State NMR Perspective

Author: Jayakrishna Shenoy, Yann Fichou, Denis Martinez, Nadia El Mammeri, Brice Kauffmann, Ahmad Saad, Mathias Ferber, Gaelle Lamon, Antoine Loquet, Estelle Morvan, Asen Daskalov, Alons Lends, Mélanie Berbon, Benjamin Bardiaux, Axelle Grélard, Birgit Habenstein, Sven J. Saupe, Bardiaux, Benjamin, Structure et fonctions de motifs amyloïdes impliqués dans la transduction du signal - - SFAS2017 - ANR-17-CE11-0035 - AAPG2017 - VALID, Amyloïdes fonctionnels formés par les hydrophobines du pathogène fongique Aspergillus fumigatus - - FUNHYDRO2016 - ANR-16-CE11-0020 - AAPG2016 - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Weak interactions in self-organizations studied by NMR spectroscopy in the supramolecular solid-state - Weakinteract - - H20202015-09-01 - 2020-09-01 - 639020 - VALID, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Soutien à la Recherche de l'Institut Européen de Chimie Biologique, Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), We acknowledge financial support from the European Research Council (ERC) under the European Unions Horizon 2020 Research and Innovation Program (ERC-2015-StG GA no. 639020 to ALo), the ANR (ANR-17-CE11-0035 to SJS and ANR-16-CE11-0020-01 to MF, GL, BB and ALo), and INCEPTION project (PIA/ANR-16-CONV-0005) to BB. AD was supported by the Nouvelle Aquitaine Regional Council. ALe was supported by the Swiss National Science Foundation for early postdoc mobility project P2EZP2_184258. This work has benefited from the facilities and expertise of the Biophysical and Structural Chemistry platform (BPCS) at IECB, CNRS UMS3033, Inserm US001, Bordeaux University., ANR-17-CE11-0035,SFAS,Structure et fonctions de motifs amyloïdes impliqués dans la transduction du signal(2017), ANR-16-CE11-0020,FUNHYDRO,Amyloïdes fonctionnels formés par les hydrophobines du pathogène fongique Aspergillus fumigatus(2016), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 639020,H2020,ERC-2014-STG,Weakinteract(2015), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Européen de Chimie et de Biologie-Université Sciences et Technologies - Bordeaux 1-Institut de Chimie du CNRS (INC), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Conformational change, Amyloid, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Neurosciences. Biological psychiatry. Neuropsychiatry, Review, Computational biology, Fibril, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, amyloid fibril, structural biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, 030304 developmental biology, 0303 health sciences, Chemistry, A protein, Pathogenicity, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Structural biology, Solid-state nuclear magnetic resonance, functional amyloids, prion structure, solid-state NMR, Protein folding, 030217 neurology & neurosurgery, RC321-571, Neuroscience
Abstract: International audience; Infectious proteins or prions are a remarkable class of pathogens, where pathogenicity and infectious state correspond to conformational transition of a protein fold. The conformational change translates into the formation by the protein of insoluble amyloid aggregates, associated in humans with various neurodegenerative disorders and systemic protein-deposition diseases. The prion principle, however, is not limited to pathogenicity. While pathological amyloids (and prions) emerge from protein misfolding, a class of functional amyloids has been defined, consisting of amyloid-forming domains under natural selection and with diverse biological roles. Although of great importance, prion amyloid structures remain challenging for conventional structural biology techniques. Solid-state nuclear magnetic resonance (SSNMR) has been preferentially used to investigate these insoluble, morphologically heterogeneous aggregates with poor crystallinity. SSNMR methods have yielded a wealth of knowledge regarding the fundamentals of prion biology and have helped to solve the structures of several prion and prion-like fibrils. Here, we will review pathological and functional amyloid structures and will discuss some of the obtained structural models. We will finish the review with a perspective on integrative approaches combining solid-state NMR, electron paramagnetic resonance and cryo-electron microscopy, which can complement and extend our toolkit to structurally explore various facets of prion biology.
Published: 2021
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18. Sensing a binding event through charge transport variations using an aromatic oligoamide capsule

Author: Gilles Pecastaings, Alejandro Méndez-Ardoy, Alice Boulloy, Brice Kauffmann, Ivan Huc, Thierry Buffeteau, Dario M. Bassani, Yann Ferrand, Antoine Jacquet, Pedro Mateus, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Polymères Organiques (LCPO), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC), ANR-19-CE18-0018,SERO6Pain,Les voies de signalisation du récepteur 5-HT6: de nouvelles cibles pour le traitement de la douleur neuropathique?(2019), European Project: 707071,H2020,H2020-MSCA-IF-2015,RAMSES(2016), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), Team 4 LCPO : Polymer Materials for Electronic, Energy, Information and Communication Technologies, Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), Ludwig-Maximilians-Universität München (LMU), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Admin, Oskar, Les voies de signalisation du récepteur 5-HT6: de nouvelles cibles pour le traitement de la douleur neuropathique? - - SERO6Pain2019 - ANR-19-CE18-0018 - AAPG2019 - VALID, and Aryl amide metallofoldamersas selective saccharide sensors - RAMSES - - H20202016-03-01 - 2018-02-28 - 707071 - VALID
Subjects: chemistry.chemical_classification, [CHIM.MATE] Chemical Sciences/Material chemistry, 010405 organic chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Carboxylic acid, Foldamer, Protonation, General Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Crystallography, chemistry.chemical_compound, Chemistry, Dicarboxylic acid, Deprotonation, chemistry, Monolayer, Tartaric acid, Molecule
Abstract: The selective binding properties of a 13-mer oligoamide foldamer capsule composed of 4 different aromatic subunits are reported. The capsule was designed to recognize dicarboxylic acids through multiple-point interactions owing to a combination of protonation/deprotonation events, H-bonding, and geometrical constraints imparted by the rigidity of the foldamer backbone. Compared to tartaric acid, binding of 2,2-difluorosuccinic acid or 2,2,3,3-tetrafluorosuccinic acid resulted in symmetry breaking due to deprotonation of only one of the two carboxylic acid groups of the encapsulated species as shown by NMR studies in solution and by single-crystal X-ray diffraction in the solid state. An analogous 14-mer foldamer capsule terminated with a thiol anchoring group was used to probe the complexation event in self-assembled monolayers on Au substrates. Ellipsometry and polarization-modulation infrared absorption-reflection spectroscopy studies were consistent with the formation of a single molecule layer of the foldamer capsule oriented vertically with respect to the surface. The latter underwent smooth complexation of 2,2-difluorosuccinic acid with deprotonation of one of the two carboxylic acid groups. A significant (80-fold) difference in the charge transport properties of the monolayer upon encapsulation of the dicarboxylic acid was evidenced from conducting-AFM measurements (S = 1.1 × 10−9vs. 1.4 × 10−11 ohm−1 for the empty and complexed capsule, respectively). The modulation in conductivity was assigned to protonation of the aromatic foldamer backbone., Conductance through a monolayer of a helical foldamer host was found to vary by 80-fold depending on the presence or the absence of a guest in the host's cavity.
Published: 2021
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19. Photophysical and Antibacterial Properties of Porphyrins Encapsulated inside Acetylated Lignin Nanoparticles

Author: Mariette M. Pereira, Nicolas Villandier, Nidia Maldonado-Carmona, Stéphanie Leroy-Lhez, Mário J. F. Calvete, Tan-Sothea Ouk, Claude Alain Calliste, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), European Project: 820196,Horizon H2020, European Project: 798205, and Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), lignin valorization, Quantum yield, Nanoparticle, RM1-950, 02 engineering and technology, 010402 general chemistry, Photochemistry, 01 natural sciences, Biochemistry, Microbiology, Article, chemistry.chemical_compound, Dynamic light scattering, Zeta potential, polycyclic compounds, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, Chemistry, Singlet oxygen, tetrapyrrolic compounds, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, Photobleaching, Porphyrin, Fluorescence, 0104 chemical sciences, Infectious Diseases, photodynamic therapy, Therapeutics. Pharmacology, 0210 nano-technology
Abstract: Lignin has recently attracted the attention of the scientific community, as a suitable raw material for biomedical applications. In this work, acetylated lignin was used to encapsulate five different porphyrins, aiming to preserve their photophysical properties, and for further use as antibacterial treatment. The obtained nanoparticles were physically characterized, through dynamic light scattering size measurement, polydispersity index and zeta potential values. Additionally, the photophysical properties of the nanoparticles, namely UV-vis absorption, fluorescence emission, singlet oxygen production and photobleaching, were compared with those of the free porphyrins. It was found that all the porphyrins were susceptible to encapsulation, with an observed decrease in their fluorescence quantum yield and singlet oxygen production. These nanoparticles were able to exert an effective photodynamic bactericide effect (blue-LED light, 450–460 nm, 15 J/cm2) on Staphylococcus aureus and Escherichia coli. Furthermore, it was achieved a photodynamic bactericidal activity on an encapsulated lipophillic porphyrin, where the free porphyrin failed to diminish the bacterial survival. In this work it was demonstrated that acetylated lignin encapsulation works as a universal, cheap and green material for the delivery of porphyrins, while preserving their photophysical properties.
Published: 2021
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20. Effects of radiofrequency field exposure on proteotoxic-induced and heat-induced HSF1 response in live cells using the bioluminescence resonance energy transfer technique

Author: Isabelle Lagroye, Denis Habauzit, Delia Arnaud-Cormos, Annabelle Hurtier, Yann Chappe, Yves Le Dréan, Catherine Martin, Hermanus J. Ruigrok, André Garenne, Emmanuelle Poque, Yann Percherancier, Philippe Lévêque, Florence Poulletier de Gannes, Chard-Hutchinson, Xavier, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), BIO-INGENIERIE (XLIM-BIO-INGENIERIE), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 603794 (the GERONIMO project), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, Radio Waves, [SDV]Life Sciences [q-bio], HSF1, Bioluminescence resonance energy transfer, Biochemistry, Signal, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Heat Shock Transcription Factors, MG132, medicine, Bioluminescence, Humans, Original Paper, Chemistry, fungi, Specific absorption rate, Cell Biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, HEK293 Cells, Energy Transfer, Cell culture, 030220 oncology & carcinogenesis, Radiofrequency, Luminescent Measurements, Biophysics, Proteasome inhibitor, Trimerization, Continuous wave, Radio frequency, Heat-Shock Response, medicine.drug
Abstract: As of today, only acute effects of RF fields have been confirmed to represent a potential health hazard and they are attributed to non-specific heating (≥ 1 °C) under high-level exposure. Yet, the possibility that environmental RF impact living matter in the absence of temperature elevation needs further investigation. Since HSF1 is both a thermosensor and the master regulator of heat-shock stress response in eukaryotes, it remains to assess HSF1 activation in live cells under exposure to low-level RF signals. We thus measured basal, temperature-induced, and chemically induced HSF1 trimerization, a mandatory step on the cascade of HSF1 activation, under RF exposure to continuous wave (CW), Global System for Mobile (GSM), and Wi-Fi-modulated 1800 MHz signals, using a bioluminescence resonance energy transfer technique (BRET) probe. Our results show that, as expected, HSF1 is heat-activated by acute exposure of transiently transfected HEK293T cells to a CW RF field at a specific absorption rate of 24 W/kg for 30 min. However, we found no evidence of HSF1 activation under the same RF exposure condition when the cell culture medium temperature was fixed. We also found no experimental evidence that, at a fixed temperature, chronic RF exposure for 24 h at a SAR of 1.5 and 6 W/kg altered the potency or the maximal capability of the proteasome inhibitor MG132 to activate HSF1, whatever signal used. We only found that RF exposure to CW signals (1.5 and 6 W/kg) and GSM signals (1.5 W/kg) for 24 h marginally decreased basal HSF1 activity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12192-020-01172-3) contains supplementary material, which is available to authorized users.
Published: 2021
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21. Carbamylation of elastic fibers is a molecular substratum of aortic stiffness

Author: Doué, Manon, Okwieka, Anaïs, Berquand, Alexandre, Gorisse, Laëtitia, Maurice, Pascal, Velard, Frédéric, Terryn, Christine, Molinari, Michaël, Duca, Laurent, Piétrement, Christine, Gillery, Philippe, Jaisson, Stéphane, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Recherche en Nanosciences - EA 4682 (LRN), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Biomatériaux et inflammation en site osseux - EA 4691 (BIOS), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Université de Reims Champagne-Ardenne (URCA), Plateforme en Imagerie Cellulaire et Tissulaire (PICT), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Reims (CHU Reims), Tis study was funded by the University of Reims Champagne-Ardenne and the Reims University Hospital through the 'Projet Hospitalo Universitaire VIeillissement protéique et VAsculaire (PHU-VIVA)' program and was also supported by grants from the Committee of American Memorial Hospital (Reims, France and Boston, MA, USA) and the Centre National de la Recherche Scientifque (CNRS, France). Te region Grand Est, the FEDERprogram, and the DRRT Grand Est are acknowledged for the funding of the Nano’Mat platform., Velard, Frédéric, SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Protein Carbamylation, Science, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Elastic Tissue, Article, Cardiovascular biology, Elastin, Atomic force microscopy, Mice, Vascular Stiffness, [SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Medicine, Animals, Cattle, Vascular diseases, Aorta, Cyanates, Chemical modification
Abstract: International audience; Because of their long lifespan, matrix proteins of the vascular wall, such as elastin, are subjected to molecular aging characterized by non-enzymatic post-translational modifications, like carbamylation which results from the binding of cyanate (mainly derived from the dissociation of urea) to protein amino groups. While several studies have demonstrated a relationship between increased plasma concentrations of carbamylated proteins and the development of cardiovascular diseases, molecular mechanisms explaining the involvement of protein carbamylation in these pathological contexts remain to be fully elucidated. The aim of this work was to determine whether vascular elastic fibers could be carbamylated, and if so, what impact this phenomenon would have on the mechanical properties of the vascular wall. Our experiments showed that vascular elastin was carbamylated in vivo. Fiber morphology was unchanged after in vitro carbamylation, as well as its sensitivity to elastase degradation. In mice fed with cyanate-supplemented water in order to increase protein carbamylation within the aortic wall, an increased stiffness in elastic fibers was evidenced by atomic force microscopy, whereas no fragmentation of elastic fiber was observed. In addition, this increased stiffness was also associated with an increase in aortic pulse wave velocity in ApoE −/− mice. These results provide evidence for the carbamylation of elastic fibers which results in an increase in their stiffness at the molecular level. These alterations of vessel wall mechanical properties may contribute to aortic stiffness, suggesting a new role for carbamylation in cardiovascular diseases.
Published: 2021
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22. Architecture and regulation of an enterobacterial cellulose secretion system

Author: Meryem Caleechurn, Petya V. Krasteva, Wiem Abidi, Stéphane Roche, Samira Zouhir, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), KRASTEVA, Petya Violinova, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein subunit, macromolecular substances, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, Structural Biology, Inner membrane, Secretion, Cellulose, Research Articles, 030304 developmental biology, 0303 health sciences, Multidisciplinary, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], ATP synthase, biology, 030306 microbiology, technology, industry, and agriculture, SciAdv r-articles, Periplasmic space, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cell biology, Intracellular Second Messenger, Cytosol, chemistry, biology.protein, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Research Article
Abstract: Structural snapshots decipher nucleotide dependence, asymmetry, and polymerization in the enterobacterial cellulose secretion., Many free-living and pathogenic enterobacteria secrete biofilm-promoting cellulose using a multicomponent, envelope-embedded Bcs secretion system under the control of intracellular second messenger c-di-GMP. The molecular understanding of system assembly and cellulose secretion has been largely limited to the crystallographic studies of a distantly homologous BcsAB synthase tandem and a low-resolution reconstruction of an assembled macrocomplex that encompasses most of the inner membrane and cytosolic subunits and features an atypical layered architecture. Here, we present cryo-EM structures of the assembled Bcs macrocomplex, as well as multiple crystallographic snapshots of regulatory Bcs subcomplexes. The structural and functional data uncover the mechanism of asymmetric secretion system assembly and periplasmic crown polymerization and reveal unexpected subunit stoichiometry, multisite c-di-GMP recognition, and ATP-dependent regulation.
Published: 2021
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23. Light-mediated chiroptical switching of an achiral foldamer host in presence of a carbohydrate guest

Author: Stefan Hecht, Ivan Huc, Susnata Pramanik, Brice Kauffmann, Yann Ferrand, FERRAND, Yann, Ludwig-Maximilians-Universität München (LMU), Soutien à la Recherche de l'Institut Européen de Chimie Biologique, Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Humboldt University Of Berlin, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Européen de Chimie et de Biologie-Université Sciences et Technologies - Bordeaux 1-Institut de Chimie du CNRS (INC), Humboldt-Universität zu Berlin, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), and École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 010405 organic chemistry, Chemistry, Stereochemistry, Metals and Alloys, Foldamer, General Chemistry, Carbohydrate, 010402 general chemistry, 01 natural sciences, Catalysis, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, chemistry.chemical_compound, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, Diarylethene, Materials Chemistry, Ceramics and Composites
Abstract: International audience; A photoresponsive diarylethene was incorporated in an achiral helical foldamer container. A carbohydrate guest was found to induce opposite handedness upon binding to the open and closed forms of the diarylethene-containing foldamer, thus enabling chiroptical switching of an achiral host mediated by a chiral guest.
Published: 2021
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24. Slow kinetic evolution of nanohelices based on gemini surfactant self-assemblies with various enantiomeric excess; chiral segregation towards a racemic mixture

Author: Emilie Pouget, Franck Artzner, Yutaka Okazaki, Thierry Buffeteau, Reiko Oda, Brice Kauffmann, Sylvain Nlate, Jie Gao, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Kyoto Institute of Technology, Soutien à la Recherche de l'Institut Européen de Chimie Biologique, Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique de Rennes (IPR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), France-Japan International Associated Laboratory, Chiral Nanostructures for Photonic Applications (LIA-CNPA), Centre National de la Recherche Scientifique Centre National de la Recherche Scientifique (CNRS), Universite de Bordeaux, JSPS Overseas Research Fellowship, Chinese Scholarship Council Fellowship, LabEx AMADEus [ANR-10-LABX-42, ANR-10-IDEX-03-02], Rennes Metropoles, ANR-10-LABX-0042,AMADEus,Advanced Materials by Design(2010), ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), Jonchère, Laurent, Advanced Materials by Design - - AMADEus2010 - ANR-10-LABX-0042 - LABX - VALID, Initiative d'excellence de l'Université de Bordeaux - - IDEX BORDEAUX2010 - ANR-10-IDEX-0003 - IDEX - VALID, École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Européen de Chimie et de Biologie-Université Sciences et Technologies - Bordeaux 1-Institut de Chimie du CNRS (INC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), and Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [PHYS]Physics [physics], 010405 organic chemistry, Chemistry, 010402 general chemistry, Kinetic energy, 01 natural sciences, 0104 chemical sciences, [PHYS] Physics [physics], Crystallography, Pulmonary surfactant, Amphiphile, Ribbon, Materials Chemistry, Racemic mixture, General Materials Science, Enantiomer, Enantiomeric excess
Abstract: International audience; Very slow kinetic evolution (days) of chiral nanoribbons based on amphiphilic molecular assemblies is investigated for various enantiomeric excess. In the early stage of ribbon formation, those formed for low enantiomeric excess (0
Published: 2021
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25. Urea based foldamers

Author: Sung Hyun Yoo, Christel Dolain, Morgane Pasco, Gilles Guichard, Bo Li, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), E. James Petersson, ANR-15-CE07-0010,CHIMPP2I,Hélices chimériques aux propriétés innovantes pour l'inhibition des interactions protéine-protéine(2015), ANR-17-CE07-0020,FOLDINGUE,Mimétisme et ingénierie d'enzymes artificielles à l'aide de foldamères(2017), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Admin, Oskar, Hélices chimériques aux propriétés innovantes pour l'inhibition des interactions protéine-protéine - - CHIMPP2I2015 - ANR-15-CE07-0010 - AAPG2015 - VALID, and Mimétisme et ingénierie d'enzymes artificielles à l'aide de foldamères - - FOLDINGUE2017 - ANR-17-CE07-0020 - AAPG2017 - VALID
Subjects: chemistry.chemical_classification, 010405 organic chemistry, Peptidomimetic, Protein Conformation, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, alpha-Helical, Molecular, Sequence (biology), Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Combinatorial chemistry, 0104 chemical sciences, Folding (chemistry), chemistry.chemical_compound, Monomer, Enantiopure drug, Solid-phase synthesis, chemistry, Models, Helix, Urea, Peptidomimetics, Peptides
Abstract: International audience; N,N'-linked oligoureas are a class of enantiopure, sequence-defined peptidomimetic oligomers without amino acids that form well-defined and predictable helical structures akin to the peptide α-helix. Oligourea-based foldamers combine a number of features-such as synthetic accessibility, sequence modularity, and folding fidelity-that bode well for their use in a range of applications from medicinal chemistry to catalysis. Moreover, it was recently recognized that this synthetic helical backbone can be combined with regular peptides to generate helically folded peptide-oligourea hybrids that display additional features in terms of helix mimicry and protein-surface recognition properties. Here we provide detailed protocols for the preparation of requested monomers and for the synthesis and purification of homo-oligoureas and peptide-oligourea hybrids.
Published: 2021
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26. Aβ(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage

Author: Emad Tajkhorshid, Eduard Puig, Sonia Ciudad, Thomas Botzanowski, Mariam Bayoumi, Vladislav Yu. Orekhov, Benjamin Bardiaux, Giovanni Maglia, Sarah Cianférani, Andres S. Arango, Stéphane Chaignepain, Jimmy Do, Moeen Meigooni, Natàlia Carulla, Maxim Mayzel, Chemical Biology 1, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, University of Gothenburg (GU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Groningen [Groningen], Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institute for Research in Biomedicine (IRB Barcelona) (IRB), Institute for Research in Biomedicine, This study was supported by MINECO (SAF2015-68789), the Fondation Recherche Médicale (AJE20151234751) and the Counseil Régional d’Aquitaine Limousin Poitou-Charentes (1R30117-00007559) to N.C. The authors G.M and N.C. acknowledge funds from Fundació La Marató de TV3 (20140730). B.B research was supported by the INCEPTION project (ANR-16-CONV-0005). E.T. was supported by the National Institutes of Health (P41-GM104601 and R01-GM123455) and also acknowledges computing resources provided by Blue Waters at National Center for Supercomputing Applications, and Extreme Science and Engineering Discovery Environment XSEDE (grant MCA06N060). V.O. research was supported by the Swedish Research Council Formas (2015-04614). S. Cianferani research was supported by Agence Nationale de la Recherche and the French Proteomic Infrastructure (ANR-10-INBS-08-03). N.C., S. Cianferani, T.B. and E.P. acknowledge the support of COST Action (BM1403). E.P. was a PhD fellow funded by MINECO (FPI). T.B. was a PhD fellow funded by Institut de Recherche Servier., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, AMYLOID-BETA-PEPTIDE, PROTEINS, Science, General Physics and Astronomy, COLLISION CROSS-SECTIONS, Conductivity, Oligomer, General Biochemistry, Genetics and Molecular Biology, Article, ATOMIC-RESOLUTION STRUCTURE, 03 medical and health sciences, Molecular dynamics, chemistry.chemical_compound, CONFORMATIONS, 0302 clinical medicine, Tetramer, Alzheimer Disease, Humans, Histone octamer, Lipid bilayer, lcsh:Science, A-BETA, Multidisciplinary, Amyloid beta-Peptides, CHANNELS, PURIFICATION, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Brain, Membrane structure and assembly, General Chemistry, Permeation, Peptide Fragments, NMR, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, ALZHEIMERS-DISEASE, 030104 developmental biology, Membrane, chemistry, Biophysics, lcsh:Q, Solution-state NMR, 030217 neurology & neurosurgery
Abstract: Formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimerʼs disease (AD). Here, we present the three-dimensional structure of an Aβ oligomer formed in a membrane mimicking environment, namely an Aβ(1-42) tetramer, which comprises a six stranded β-sheet core. The two faces of the β-sheet core are hydrophobic and surrounded by the membrane-mimicking environment while the edges are hydrophilic and solvent-exposed. By increasing the concentration of Aβ(1-42) in the sample, Aβ(1-42) octamers are also formed, made by two Aβ(1-42) tetramers facing each other forming a β-sandwich structure. Notably, Aβ(1-42) tetramers and octamers inserted into lipid bilayers as well-defined pores. To establish oligomer structure-membrane activity relationships, molecular dynamics simulations were carried out. These studies revealed a mechanism of membrane disruption in which water permeation occurred through lipid-stabilized pores mediated by the hydrophilic residues located on the core β-sheets edges of the oligomers., Formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimer´s disease. Here authors present the 3D- structure of an Aβ oligomer formed in a membrane mimicking environment and observe that Aβ tetramers and octamers inserted into lipid bilayers as well-defined pores.
Published: 2020
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27. Identification of NLR-associated amyloid signaling motifs in bacterial genomes

Author: Mélanie Berbon, Antoine Loquet, Witold Dyrka, Thierry Bardin, Alons Lends, Sven J. Saupe, Bénédicte Salin, Corinne Blancard, Brice Kauffmann, Virginie Coustou, Asen Daskalov, Politechnika Wroclawska [Wrocław], Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), University of California [Berkeley], University of California, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Coustou, virginie, University of California [Berkeley] (UC Berkeley), University of California (UC), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Amyloid, Prions, [SDV]Life Sciences [q-bio], Amino Acid Motifs, Amyloidogenic Proteins, NLR Proteins, Bacterial genome size, Cyanobacteria, Conserved sequence, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Structural Biology, Animals, Amino Acid Sequence, Molecular Biology, Gene, 030304 developmental biology, Genetics, 0303 health sciences, biology, C-terminus, Fungi, biology.organism_classification, Immunity, Innate, N-terminus, [SDV] Life Sciences [q-bio], Multicellular organism, Drosophila, Signal transduction, Genome, Bacterial, 030217 neurology & neurosurgery, Bacteria, Signal Transduction
Abstract: International audience; In filamentous fungi, amyloid signaling sequences allow Nod-like receptors (NLRs) to activate downstream cell-death inducing proteins with HeLo and HeLo-like (HELL) domains and amyloid RHIM and RHIM-related motifs control immune defense pathways in mammals and flies. Herein, we show bioinformatically that analogous amyloid signaling motifs exist in bacteria. These short motifs are found at the N-terminus of NLRs and at the C-terminus of proteins with a domain we term BELL. The corresponding NLR and BELL proteins are encoded by adjacent genes. We identify 10 families of such bacterial amyloid signaling sequences (BASS), one of which (BASS3) is homologous to RHIM and a fungal amyloid motif termed PP. BASS motifs occur nearly exclusively in bacteria forming multicellular structures (mainly in Actinobacteria and Cyanobacteria). We analyze experimentally a subset of seven of these motifs (from the most common BASS1 family and the RHIM-related BASS3 family) and find that these sequences form fibrils in vitro. Using a fungal in vivo model, we show that all tested BASS-motifs form prions and that the NLR-side motifs seed prion-formation of the corresponding BELL-side motif. We find that BASS3 motifs show partial prion cross-seeding with mammalian RHIM and fungal PP-motifs and that proline mutations on key positions of the BASS3 core motif, conserved in RHIM and PP-motifs, abolish prion formation. This work expands the paradigm of prion amyloid signaling to multicellular prokaryotes and suggests a long-term evolutionary conservation of these motifs from bacteria, to fungi and animals.
Published: 2020
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28. ELA/APELA precursor cleaved by furin displays tumor suppressor function in renal cell carcinoma through mTORC1 activation

Author: Abdel-Majid Khatib, Jean Descarpentrie, Malaurie Eugenie, Amandine Mouchard, Juan A. Rosado, Mercedes Tomé, Isabelle Soubeyran, Jean-Luc Hoepffner, Isabel D. Alves, Macha Nikolski, Jose J. Lopez, Raúl V. Durán, Serge Evrard, Marielle Dubreuil, Geraldine Siegfried, Bruno O. Villoutreix, Katarzyna B. Hooks, Clément Bodineau, Fabienne Soulet, Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire de pharmacologie expérimentale et clinique : cibles moléculaires en cancérologie ((U 716)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ligue Nationale contre le Cancer (France), Conseil régional d'Aquitaine, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Angiogenesis, Peptide Hormones, [SDV]Life Sciences [q-bio], Chromophobe Renal Cell Carcinoma, mTORC1, Mechanistic Target of Rapamycin Complex 1, Biology, Kidney, Mice, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Sunitinib, medicine, Animals, Humans, Carcinoma, Renal Cell, Furin, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, Apelin receptor, Apelin Receptors, Cell growth, Tumor Suppressor Proteins, General Medicine, 3. Good health, Apelin, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Intercellular Signaling Peptides and Proteins, Calcium, Signal Transduction, Research Article
Abstract: Apelin is a well-established mediator of survival and mitogenic signaling through the apelin receptor (Aplnr) and has been implicated in various cancers; however, little is known regarding Elabela (ELA/APELA) signaling, also mediated by Aplnr, and its role and the role of the conversion of its precursor proELA into mature ELA in cancer are unknown. Here, we identified a function of mTORC1 signaling as an essential mediator of ELA that repressed kidney tumor cell growth, migration, and survival. Moreover, sunitinib and ELA showed a synergistic effect in repressing tumor growth and angiogenesis in mice. The use of site-directed mutagenesis and pharmacological experiments provided evidence that the alteration of the cleavage site of proELA by furin induced improved ELA antitumorigenic activity. Finally, a cohort of tumors and public data sets revealed that ELA was only repressed in the main human kidney cancer subtypes, namely clear cell, papillary, and chromophobe renal cell carcinoma. Aplnr was expressed by various kidney cells, whereas ELA was generally expressed by epithelial cells. Collectively, these results showed the tumor-suppressive role of mTORC1 signaling mediated by ELA and established the potential use of ELA or derivatives in kidney cancer treatment., This work was supported by INSERM, SIRIC Brio, Region Nouvelle Aquitaine, and La Ligue Contre le Cancer.
Published: 2020
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29. Optimal Anchoring of a Urea-based Foldamer Inhibitor of ASF1 Histone Chaperone Through Backbone Plasticity

Author: May Bakail, Seydou Traoré, Céline Douat, Gilles Guichard, Johanne Mbianda, Raphael Guerois, Marie E. Perrin, François Becher, Christophe André, Françoise Ochsenbein, Pierre Legrand, Gwenaëlle Moal, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire d'immuno-allergie alimentaire (LI2A), Institut National de la Recherche Agronomique (INRA)-Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay, Université Panthéon-Sorbonne (UP1), Centre Régional AGRHYMET (CRA), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assemblage moléculaire et intégrité du génome (AMIG), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), and Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: chemistry.chemical_classification, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Peptidomimetic, Chemistry, Foldamer, Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Chromatin, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Folding (chemistry), [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Histone, Chaperone (protein), [CHIM.CRIS]Chemical Sciences/Cristallography, biology.protein, Biophysics, Side chain
Abstract: Sequence-specific oligomers with predictable folding patterns, i.e. foldamers provide new opportunities to mimic α-helical peptides and design inhibitors of protein-protein interactions. One major hurdle of this strategy is to retain the correct orientation of key side chains involved in protein surface recognition. Here, we show that the structural plasticity of a foldamer backbone may significantly contribute to the required spatial adjustment for optimal interaction with the protein surface. By using oligoureas as α-helix mimics, we designed a foldamer/peptide hybrid inhibitor of histone chaperone ASF1, a key regulator of chromatin dynamics. The crystal structure of its complex with ASF1 reveals a striking plasticity of the urea backbone, which adapts to the ASF1 surface to maintain the same binding interface. One additional benefit of generating ASF1 ligands with non-peptide oligourea segments is the resistance to proteolysis in human plasma which was highly improved compared to the cognate α-helical peptide.
Published: 2020
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30. Characterization of the DNA and Membrane Interactions of a Bioreducible Cell-Penetrating Foldamer in its Monomeric and Dimeric Form

Author: Gilles Guichard, Burkhard Bechinger, Céline Douat, Christopher Aisenbrey, Antoine Kichler, Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Aisenbrey, Christopher, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Steric effects, Polymers, Dimer, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, chemistry.chemical_compound, 0103 physical sciences, Materials Chemistry, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS, 010304 chemical physics, Chemistry, Foldamer, DNA, Transfection, Hydrogen-Ion Concentration, 0104 chemical sciences, Surfaces, Coatings and Films, Membrane, Monomer, Covalent bond, Biophysics, Thermodynamics, Dimerization
Abstract: The biophysical properties of a designed bioreducible oligourea foldamer, which shows excellent transfection activities in its dimeric form are presented. Binding isotherms of the monomer as well as of the dimer to both DNA and lipid membranes were determined by indole fluorescence. Comparing the monomer with the dimer allows both a precise biophysical characterization of the role of dimerization and characterization of how the covalent linkage between two monomers affects the transfection activity. The results indicate that dimerization results in pronounced changes in the thermodynamics of different steps of the transfection process, which extend well beyond simple steric effects within the dimer. A model emerges where the imidazole-containing polymers compact DNA at neutral pH, but they liberate the polyurea from the DNA complex at low pH, thus being able to rupture acidified endosomes. Indeed, the dimerization inverts the pH dependence of the binding affinities toward the requirements suggested by this model for efficient transfection.
Published: 2020
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31. Cholesterol impacts chemokine CCR5 receptor ligand‐binding activity

Author: Pierre Calmet, Maylou Vang, Sandra Cortès, Jean Dessolin, Sophie Lecomte, Nada Taib Maamar, Rim Baccouch, Nada Caudy, Isabel D. Alves, Bruno Tillier, Christophe Cullin, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Synthelis, Laboratoire de Physiogénomique / NeuroTranscriptomes et Paléogénétique (LPG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Flluorescence anisotropy, Chemokine, Allosteric modulator, Receptors, CCR5, Chemokine receptor CCR5, medicine.drug_class, HIV Infections, HIV Envelope Protein gp120, Ligands, Biochemistry, Maraviroc, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pichia pastoris, medicine, Humans, [CHIM]Chemical Sciences, Receptor, Molecular Biology, Cell free expression, Plasmon waveguide resonance, ComputingMilieux_MISCELLANEOUS, G protein-coupled receptor, biology, Chemistry, HIV, Chemokine CCR5 receptor, Cell Biology, Surface Plasmon Resonance, Virus Internalization, Receptor antagonist, Ligand (biochemistry), Cell biology, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 030104 developmental biology, Cholesterol, 030220 oncology & carcinogenesis, Saccharomycetales, biology.protein, Receptors, Virus
Abstract: International audience; AbstractBackground/AimsThe chemokine CCR5 receptor is target of maraviroc, a negative allosteric modulator of CCR5 that blocks the HIV protein gp120 from associating with the receptor, thereby inhibiting virus cellular entry. As noted with other GPCR family members, the role of the lipid environment in CCR5 signaling remains obscure and very modestly investigated. Controversial literature on the impact of cholesterol depletion in HIV infection and CCR5 signaling, including the hypothesis that cholesterol depletion could inhibit HIV infection, lead us to focus on the understanding of cholesterol impact in the first stages of receptor activation.MethodsTo address this aim, the approach chosen was to employ reconstituted model lipid systems of controlled lipid composition containing CCR5 from two distinct expression systems: P. pastoris and cell‐free expression. The characterization of receptor/ligand interaction in terms of total binding or competition binding assays was independently performed by Plasmon Waveguide Resonance and Fluorescence Anisotropy, respectively. Maraviroc, a potent receptor antagonist was the ligand investigated. Additionally, Coarse‐grained Molecular Dynamics Simulation was employed to investigate cholesterol impact in the receptor conformational flexibility and dynamics.ResultsResults obtained with receptor produced by different expression systems and using different biophysical approaches clearly demonstrate a considerable impact of cholesterol in the binding affinity of maraviroc to the receptor and receptor conformational dynamics. Conclusion: Cholesterol considerably decreases maraviroc binding affinity to the CCR5 receptor. The mechanisms by which this effect occurs seems to involve the adoption of distinct receptor conformational states with restrained structural dynamics and helical motions in the presence of cholesterol.
Published: 2020
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32. Connecting the dots: from nanodomains to physiological functions of REMORINs

Author: Birgit Habenstein, Anthony Legrand, Julien Gronnier, Marie-Dominique Jolivet, Paul Gouguet, Anne-Flore Deroubaix, Sylvie German-Retana, Sébastien Mongrand, Marie Boudsocq, Artemis Perraki, Véronique Germain, Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), University of Tübingen, Department of Plant and Microbial Biology [Zurich, Suisse], Universität Zürich [Zürich] = University of Zurich (UZH), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Department of Plant Sciences, University of Cambridge, Cambridge, UK, Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French Ministère de l’Enseignement Supérieur et de la Recherche (MESR). EMBO LTF 438-2018 and ERC-2017-COG IMMUNO-PEPTALK ID: 773153. CNRS Momentum., ANR-19-CE13-0021,PhosphoREM-domain,Régulation de la communication intercellulaire - le rôle de la phosphoprotéine REMORIN liée aux nanodomaines de la membrane plasmique(2019), ANR-16-CE20-0008,PotyMove,Facteurs cellulaires recrutés par les potyvirus pour leur transport intercellulaire : de nouvelles sources de résistance des plantes?(2016), ANR-10-LABX-0040,SPS,Saclay Plant Sciences(2010), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Cambridge [UK] (CAM), and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, Remorins, Protein family, Physiology, [SDV]Life Sciences [q-bio], Arabidopsis, Pathologie végétale, Plant Science, Computational biology, Biology, 01 natural sciences, 03 medical and health sciences, Membrane Microdomains, santé des plantes, mental disorders, Genetics, Focus Issue on Dynamic Membranes, Hormone signaling, 030304 developmental biology, Plant Proteins, 0303 health sciences, Interaction plante pathogène, Arabidopsis Proteins, musculoskeletal, neural, and ocular physiology, Cell Membrane, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, Phosphorylation, virologie végétale, psychological phenomena and processes, 010606 plant biology & botany
Abstract: REMORINs (REMs) are a plant-specific protein family, proposed regulators of membrane-associated molecular assemblies and well-established markers of plasma membrane nanodomains. REMs play a diverse set of functions in plant interactions with pathogens and symbionts, responses to abiotic stresses, hormone signaling and cell-to-cell communication. In this review, we highlight the established and more putative roles of REMs throughout the literature. We discuss the physiological functions of REMs, the mechanisms underlying their nanodomain-organization and their putative role as regulators of nanodomain-associated molecular assemblies. Furthermore, we discuss how REM phosphorylation may regulate their functional versatility. Overall, through data-mining and comparative analysis of the literature, we suggest how to further study the molecular mechanisms underpinning the functions of REMs.
Published: 2020
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33. Regulation of podosome formation in aortic endothelial cells vessels by physiological extracellular cues

Author: Elisabeth Génot, Filipa Curado, Isabelle Fremaux, Thomas Daubon, Isabel Egaña, Marion Decossas, Florian Alonso, Pirjo Spuul, Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Cell type, Histology, Podosome, Endothelial cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, Microfilament, Vascular biology, Pathology and Forensic Medicine, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Humans, Cell adhesion, Cytoskeleton, Aorta, Chemistry, Cell migration, Cell Biology, General Medicine, Cell biology, Endothelial stem cell, 030104 developmental biology, 030220 oncology & carcinogenesis, Podosomes
Abstract: International audience; Invadosomes are specialised actin-based dynamic microdomains of the plasma membrane. Their occurrence has been associated with cell adhesion, matrix degrading and mechanosensory functions that make them crucial regulators of cell migration and invasion. Monocytic, cancer cell and Src-transformed cell invadosomes have been extensively described. Less well defined are the structures which form in other cell types, i.e., non-haematopoietic and non-transformed cells, exposed to specific stimuli. We herein describe the specificities of podosomes induced in aortic endothelial cells stimulated with TGFβ in vitro and in conditions that more closely resemble the in vivo situation. These podosomes display the typical architecture of monocytic podosomes. They organise into large rosette-shape superstructures where they exhibit collective dynamic behavior consisting in cycles of formation and regression. At the ultrastructural level, microfilament arrangements in individual podosomes were revealed. Oxygen levels and hemodynamic forces, which are key players in endothelial cell biology, both influence the process. In 3D environment, podosomes appear as globular structures along cellular extensions. A better characterization of endothelial podosomes has far-reaching implications in the understanding and, possibly, in the treatment of some vascular diseases.
Published: 2020
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34. Heat-Triggered Crystallization of Liquid Crystalline Macrocycles Allowing for Conductance Switching through Hysteretic Thermal Phase Transitions

Author: Takanori Fukushima, Takashi Kajitani, Estelle Morvan, Tomoyuki Akutagawa, Norihisa Hoshino, Kota Nabeya, Kazushi Kinbara, Axelle Grélard, Tatsuya Shima, Takahiro Muraoka, Erick J. Dufourc, Department of Life Science and Technology [Yokohama, Japan], Tokyo Institute of Technology [Tokyo] (TITECH), PRESTO [Saitama, Japan] (JSTA), Japan Science and Technology Agency (JST), Institute of Multidisciplinary Research for Advanced Materials [Sendai, Japan], Tohoku University [Sendai], Laboratory for Chemistry and Life Science [Yokohama, Japan] (Institute of Innovative Research), RIKEN SPring-8 Center [Hyogo] (RIKEN RSC), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Soutien à la Recherche de l'Institut Européen de Chimie Biologique, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Européen de Chimie et de Biologie-Université Sciences et Technologies - Bordeaux 1-Institut de Chimie du CNRS (INC), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), This work was partially supported by Grant-in-Aid for Scientific Research on Innovative Areas 'Molecular Engine (No.8006)' (18H05419 and 18H05418 to KK), Grant-in-Aid for Scientific Research B (16H04129 to KK), Grant-in-Aid for Scientific Research on Innovative Areas 'p-System Figuration (No.2601)' (26102001 to TM, TF and TA), Grant-in-Aid for Young Scientists A (17H04885 to TM), JST PRESTO program 'Molecular Technology and Creation of New Functions' (to TM), and the Management Expenses Grants for National Universities Corporations from MEXT., Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CASTEX, Stéphanie, and Admin, Oskar
Subjects: Phase transition, 010402 general chemistry, 01 natural sciences, Biochemistry, isomerization, law.invention, Crystal, Crystallinity, liquid crystals, Liquid crystal, law, Phase (matter), [CHIM] Chemical Sciences, Amphiphile, [CHIM]Chemical Sciences, Crystallization, amphiphiles, 010405 organic chemistry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Conductance, General Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, 0104 chemical sciences, Crystallography, macrocycles, polymorphisms
Abstract: International audience; A polymesomorphic thermal phase-transition of a macrocyclic amphiphile consisting of aromatic groups and oligoethylene glycol (OEG) chains is reported. The macrocyclic amphiphile exists in a highly-ordered liquid crystal (LC) phase at room temperature. Upon heating, this macrocycle shows phase-transition from columnar-lamellar to nematic LC phases followed by crystallization before melting. Spectroscopic studies suggest that the thermally induced crystallization is triggered by a conformational change at the OEG chains. Interestingly, while the macrocycle returns to the columnar-lamellar phase after cooling from the isotropic liquid, it retains the crystallinity after cooling from the thermally-induced crystal. Thanks to this bistability, conductance switching was successfully demonstrated. A different macrocyclic amphiphile also shows an analogous phase-transition behavior, suggesting that this molecular design is universal for developing switchable and memorizable materials, by means of hysteretic phase-transition processes.
Published: 2018
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35. Biomol NMR Assign

Author: Gavin W. Collie, Gilles Guichard, Cameron D. Mackereth, Antoine Baudin, Antoine Loquet, Stéphane Chaignepain, Anne Guichard, Benoit Odaert, Mélanie Berbon, Agnès Hocquellet, Sabrina Rousseau, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Santé publique et épidémiologie des déterminants professionnels et sociaux de la santé, Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Européen de Chimie et Biologie, Biotechnologie des protéines recombinantes à visée santé, Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), ARNA - Acides Nucléiques : Régulations Naturelle et Artificielle, Ligue Contre le Cancer, Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Programmed cell death, TRAIL, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, 03 medical and health sciences, NMR spectroscopy, 0302 clinical medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Structural Biology, Secondary structure, DR5, Receptor, Protein secondary structure, ComputingMilieux_MISCELLANEOUS, Cancer, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, Nuclear magnetic resonance spectroscopy, Ligand (biochemistry), 3. Good health, Cell biology, 030104 developmental biology, Resonance assignment, 030220 oncology & carcinogenesis, Death-inducing signaling complex, Cancer cell
Abstract: Death receptors (DR) selectively drive cancer cells to apoptosis upon binding to the Tumor necrosis factor-a-Related Apoptosis-Inducing Ligand (TRAIL). Complex formation induces the oligomerization of the death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2) and transduces the apoptogenic signal to their respective death domains, leading to Death Inducing Signaling Complex (DISC) formation, caspase activation and ultimately cell death. Several crystal structures of the ExtraCellular Domain from Death Receptor 5 (DR5-ECD) have been reported in complex with the TRAIL ligand or anti-DR5 antibodies, but none for the isolated protein. In order to fill this gap and to perform binding experiments with TRAIL peptidomimetics, we have produced isotopically labelled DR5-ECD and started a conformational analysis by using high-field 3D NMR spectroscopy. Herein, we present the first resonance assignment of a TRAIL receptor in solution and the determination of its secondary structure from NMR chemical shifts.
Published: 2018
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36. Controlling Dipole Orientation through Curvature: Aromatic Foldamer Bent β-Sheets and Helix–Sheet–Helix Architectures

Author: Laure Sebaoun, Barbara Wicher, Yann Ferrand, Arthur Lamouroux, Victor Maurizot, Brice Kauffmann, Ivan Huc, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Chemistry, Aryl, Bent molecular geometry, Foldamer, General Chemistry, 010402 general chemistry, Curvature, 01 natural sciences, Biochemistry, Catalysis, 0104 chemical sciences, Turn (biochemistry), Folding (chemistry), Crystallography, chemistry.chemical_compound, Colloid and Surface Chemistry, Intramolecular force, Helix
Abstract: International audience; The helix, turn and beta-strand motifs of biopolymer folded structures have been found to prevail also in non-natural backbones. In contrast, foldamers with aryl rings in their main chains possess distinct conformations that may give access to folded objects beyond the reach of peptidic and nucleotidic backbones. In search for such original architectures we have explored the effect of bending aromatic amide beta-sheets using building blocks that impart curvature. Cyclic and multi-turn noncyclic sequences were synthesized and their structures were characterized in solution and in the solid state. Stable bent-sheet conformations were shown to prevail in chlorinated solvents. In these structures, folding overcomes intramolecular electrostatic repulsions and forces local dipoles in each layer of the stacked strands to align in a parallel fashion. Sequences having helical segments flanking a central bent aromatic beta-sheet were then synthesized and shown to form well-defined helix-turn-helix architectures in which helical and sheet sub-components conserve their respective integrity. These objects have a unique basket shape; they possess a cavity the depth and width of which reflects the curvature of the beta-sheet segment. They can be compared to previously described helical closed-shell receptors in which a window has been open thus providing a means to control guest binding and release pathways and kinetics. As a proof of concept, guest binding to one of the helix-sheet-helix structure is indeed found to be fast on the NMR time scale while it is generally slow in the case of helical capsules.
Published: 2017
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37. Quantitative trait loci in pepper control the effective population size of two RNA viruses at inoculation

Author: Elsa Rousseau, Alain Palloix, Frédéric Grognard, Ludovic Mailleret, Sebastien Barraillé, Marion Szadkowski, Benoît Moury, Lucie Tamisier, Frédéric Fabre, Ghislaine Nemouchi, Unité de Pathologie Végétale (PV), Institut National de la Recherche Agronomique (INRA), Génétique et Amélioration des Fruits et Légumes (GAFL), Institut Sophia Agrobiotech (ISA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Biological control of artificial ecosystems (BIOCORE), Laboratoire d'océanographie de Villefranche (LOV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche en Santé Végétale (INRA/ENITA) (UMRSV), Institut National de la Recherche Agronomique (INRA)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut des Sciences de la Vigne et du Vin (ISVV), BAP (Biologie et Amélioration des Plantes) department, SMaCH (Sustainable Management of Crop Health) metaprogramme of INRA, Région Provence-Alpes-Côte d’Azur (PACA), Station de Pathologie Végétale (AVI-PATHO), Unité de recherche Génétique et amélioration des fruits et légumes (GALF), Institut Sophia Agrobiotech [Sophia Antipolis] (ISA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'océanographie de Villefranche (LOV), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité de pathologie végétale (UR 407) INRA Avignon, Unité Mixte de Recherche en Santé Végétale (INRA/ENITA) (UMR SAVE), Institut des Sciences de la Vigne et du Vin (ISVV)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Capsicum annuum, 0106 biological sciences, 0301 basic medicine, [SDV]Life Sciences [q-bio], Potyvirus, Population, Quantitative trait locus, Cucumovirus, 01 natural sciences, Virus, Cucumber mosaic virus, 03 medical and health sciences, Virology, virus infection, bottlenecks, Potato virus Y, education, Gene, ComputingMilieux_MISCELLANEOUS, Plant Diseases, Genetics, education.field_of_study, biology, fungi, food and beverages, biology.organism_classification, Plant Leaves, 030104 developmental biology, quantitative trait loci, Capsicum, effective population size, 010606 plant biology & botany
Abstract: We thank the staff of the INRAE Experimental facilities of the Plant Pathology research unit (IEPV, https://doi.org/10.15454/8DGF-QF70) for their involvement in field experiments; International audience; Infection of plants by viruses is a complex process involving several steps: inoculation into plant cells, replication in inoculated cells and plant colonization. The success of the different steps depends, in part, on the viral effective population size (Ne), defined as the number of individuals passing their genes to the next generation. During infection, the virus population will undergo bottlenecks, leading to drastic reductions in Ne and, potentially, to the loss of the fittest variants. Therefore, it is crucial to better understand how plants affect Ne. We aimed to (i) identify the plant genetic factors controlling Ne during inoculation, (ii) understand the mechanisms used by the plant to control Ne and (iii) compare these genetic factors with the genes controlling plant resistance to viruses. Ne was measured in a doubled-haploid population of Capsicum annuum. Plants were inoculated with either a Potato virus Y (PVY) construct expressing the green fluorescent protein or a necrotic variant of Cucumber mosaic virus (CMV). Newas assessed by counting the number of primary infection foci on cotyledons for PVY or the number of necrotic local lesions on leaves for CMV. The number of foci and lesions was correlated (r=0.57) and showed a high heritability (h2=0.93 for PVY and h2=0.98 for CMV). The Ne of the two viruses was controlled by both common quantitative trait loci (QTLs) and virus-specific QTLs, indicating the contribution of general and specific mechanisms. The PVY-specific QTL colocalizes with a QTL that reduces PVY accumulation and the capacity to break down a major-effect resistance gene.
Published: 2017
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38. New tumor suppressor microRNAs target glypican-3 in human liver cancer

Author: Nathalie Dugot-Senant, Flora Cartier, Sarah Lesjean, Justine Charpentier, Amani Ghousein, Emilie Indersie, Martin Hagedorn, Angélique Desplat, Véronique Trézéguet, Christophe Grosset, Katarzyna B. Hooks, Francis Sagliocco, Grosset, Christophe, Initiative d'excellence de l'Université de Bordeaux - - IDEX BORDEAUX2010 - ANR-10-IDEX-0003 - IDEX - VALID, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Biothérapies des maladies génétiques et cancers, TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the French National Cancer Institute (grants INCa_5828/INCa_ PLBIO_2012_110 and INCa_TRANSLA_2013_209) to CFG and VT, the French Ministry of Health (grant n°DGOS/PF4/0013/105) to CFG, the Fondation pour la Recherche Médicale (FRM, grant n°DBI20131228566) to CFG, the Ligue Nationale contre le Cancer (LNCC) to CFG and VT, the Cancéropôle Grand Sud-Ouest to CFG and VT, the French State in the frame of the 'Investments for the future' Programme IdEx Bordeaux (grant ANR10-IDEX-03-02) to KBH and the charity associations Eva Pour La Vie, Aidons Marina, Fondation Flavien and E.S.CA.PE to MH and CFG., ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), Flow Cytometry Facility / TransBioMed Core [Bordeaux] (INSERM US005 - CNRS UMS 3427 - UB), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), and ANR-10-IDEX-0003-02/10-IDEX-0003,IDEX BORDEAUX,IdEx Bordeaux(2010)
Subjects: Adult, Male, 0301 basic medicine, Hepatoblastoma, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Adolescent, [SDV]Life Sciences [q-bio], Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, liver, Glypican 3, Young Adult, 03 medical and health sciences, Glypicans, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, microRNA, medicine, Humans, cancer, Genes, Tumor Suppressor, Aged, Cell Proliferation, Oncogene, Liver Neoplasms, Wnt signaling pathway, Cancer, hepatocellular carcinoma, Middle Aged, medicine.disease, glypican-3, 3. Good health, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, Oncology, Cancer research, Female, Signal transduction, Liver cancer, Research Paper
Abstract: International audience; Glypican-3 (GPC3) is an oncogene, frequently upregulated in liver malignancies such as hepatocellular carcinoma (HCC) and hepatoblastoma and constitutes a potential molecular target for therapy in liver cancer. Using a functional screening system, we identified 10 new microRNAs controlling GPC3 expression in malignant liver cells, five of them e.g. miR-4510, miR-203a-3p, miR-548aa, miR-376b-3p and miR-548v reduce GPC3 expression. These 5 microRNAs were significantly downregulated in tumoral compared to non-tumoral liver and inhibited tumor cell proliferation. Interestingly, miR-4510 inversely correlated with GPC3 mRNA and protein in HCC samples. This microRNA also induced apoptosis of hepatoma cells and blocked tumor growth in vivo in the chick chorioallantoic membrane model. We further show that the tumor suppressive effect of miR-4510 is mediated through direct targeting of GPC3 mRNA and inactivation of Wnt/β-catenin transcriptional activity and signaling pathway. Moreover, miR-4510 up-regulated the expression of several tumor suppressor genes while reducing the expression of other pro-oncogenes. In summary, we uncovered several new microRNAs targeting the oncogenic functions of GPC3. We provided strong molecular, cellular and in vivo evidences for the tumor suppressive activities of miR-4510 bringing to the fore the potential value of this microRNA in HCC therapy.
Published: 2017
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39. MRI assessment of multiple dipolar relaxation time ( T 1 D ) components in biological tissues interpreted with a generalized inhomogeneous magnetization transfer (ihMT) model

Author: Carvalho, Victor N.D., Hertanu, Andreea, Grélard, Axelle, Mchinda, Samira, Soustelle, Lucas, Loquet, Antoine, Dufourc, Erick J., Varma, Gopal, Alsop, David C., Thureau, Pierre, Girard, Olivier M., Duhamel, Guillaume, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Beth Israel Deaconess - Harvard Medical School, ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), ANR-17-CE18-0030,verISMO,IRM du transfert d'aimantation inhomogène : vers un nouveau biomarqueur in vivo spécifique et sensible de la myéline(2017), European Project: 713750,H2020,H2020-MSCA-COFUND-2015,DOC2AMU(2016), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: T 1D, MRI contrast, Myelin, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Jeener-Broekaert, Dipolar relaxation time, Inhomogeneous magnetization transfer, Myelin Imaging, ihMT
Abstract: International audience; T 1D , the relaxation time of dipolar order, is sensitive to slow motional processes. Thus T 1D is a probe for membrane dynamics and organization that could be used to characterize myelin, the lipid-rich membrane of axonal fibers. A mono-component T 1D model associated with a modified ihMT sequence was previously proposed for in vivo evaluation of T 1D with MRI. However, experiments have suggested that myelinated tissues exhibit multiple T 1D components probably due to a heterogeneous molecular mobility. A bi-component T 1D model is proposed and implemented. ihMT images of ex-vivo, fixed rat spinal cord were acquired with multiple frequency alternation rate. Fits to data yielded two T 1D s of about 500 µs and 10 ms. The proposed model seems to further explore the complexity of myelin organization compared to the previously reported mono-component T 1D model.
Published: 2020
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40. Interaction of the Anti-Proliferative GPER Inverse Agonist ERα17p with the Breast Cancer Cell Plasma Membrane: From Biophysics to Biology

Author: Delphine Ravault, Marcello Maggiolini, Lucie Khemtémourian, Isabel D. Alves, Sandrine Sagan, Mathilde Belnou, Michaël Trichet, Yves Jacquot, Lilian Shadai Salazar Vazquez, Rosamaria Lappano, Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Institut National de la Santé et de la Recherche Médicale (INSERM)-Chimie Moléculaire de Paris Centre (FR 2769), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Sorbonne Université (SU), Microscopie Electronique [IBPS] (IBPS-ME), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università della Calabria [Arcavacata di Rende] (Unical), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Chimie médicinale et recherche translationnelle (ERL Inserm U1268), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Trichet, Michaël
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Lipid Bilayers, Beta sheet, Estrogen receptor, Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Receptors, G-Protein-Coupled, 0302 clinical medicine, Lipid bilayer, Receptor, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, [CHIM.ORGA]Chemical Sciences/Organic chemistry, General Medicine, 3. Good health, Membrane, Receptors, Estrogen, 030220 oncology & carcinogenesis, MCF-7 Cells, Female, medicine.symptom, GPER, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Article, Biophysical Phenomena, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Microscopy, Electron, Transmission, apoptotic peptide, medicine, Humans, membrane interaction, Cell Proliferation, Cell Membrane, Estrogen Receptor alpha, Surface Plasmon Resonance, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Peptide Fragments, lipid vesicles, internalization, 030104 developmental biology, lcsh:Biology (General), Mechanism of action, chemistry, aggregates, Biophysics, breast cancer cells
Abstract: The peptide ER&alpha, 17p, which corresponds to the 295-311 fragment of the hinge/AF2 domains of the human estrogen receptor &alpha, (ER&alpha, ), exerts apoptosis in breast cancer cells through a mechanism involving the G protein-coupled estrogen-dependent receptor GPER. Besides this receptor-mediated mechanism, we have detected a direct interaction (Kd value in the micromolar range) of this peptide with lipid vesicles mimicking the plasma membrane of eukaryotes. The reversible and not reversible pools of interacting peptide may correspond to soluble and aggregated membrane-interacting peptide populations, respectively. By using circular dichroism (CD) spectroscopy, we have shown that the interaction of the peptide with this membrane model was associated with its folding into &beta, sheet. A slight leakage of the 5(6)-fluorescein was also observed, indicating lipid bilayer permeability. When the peptide was incubated with living breast cancer cells at the active concentration of 10 &mu, M, aggregates were detected at the plasma membrane under the form of spheres. This insoluble pool of peptide, which seems to result from a fibrillation process, is internalized in micrometric vacuoles under the form of fibrils, without evidence of cytotoxicity, at least at the microscopic level. This study provides new information on the interaction of ER&alpha, 17p with breast cancer cell membranes as well as on its mechanism of action, with respect to direct membrane effects.
Published: 2020
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41. Total Internal Reflection Tip-Enhanced Raman Spectroscopy of Cytochrome C

Author: David Talaga, Andrew Bremner, Thierry Buffeteau, Renaud Vallée, Sophie Lecomte, Sébastien Bonhommeau, Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Paul Pascal (CRPP), Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), European Project, Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], parasitic diseases, biochemical phenomena, metabolism, and nutrition, digestive system
Abstract: International audience; Surface and tip-enhanced Raman spectroscopies in total internal reflection (TIR-SERS and TIR-TERS) are used to characterize the oxidation, spin and ligation state of cytochrome C (Cc) molecules electrostatically bound on hydrophilic thiol self-assembled monolayer. TIR-SERS spectra of this model hemoprotein show marker bands typical of the 6cLS ferric state of Cc. The performances of the TIR-TERS technique as a function of the incidence angle are described, showing in particular a significant electromagnetic enhancement of the Raman signal under p-polarized light excitation. TIR-TERS spectra of Cc confirm the 6cLS ferric state assignment deduced from TIR-SERS spectra, thus demonstrating the possibility to
Published: 2020

42. Special issue Proceedings of 31st International Symposium on Chirality, Bordeaux, 2019

Author: Jeanne Crassous, Gennaro Pescitelli, Nina Berova, Reiko Oda, Oliver Trapp, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Columbia University [New York], University of Pisa - Università di Pisa, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Technical University of Munich (TUM), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pharmacology, Theoretical physics, Chemistry, Organic Chemistry, Drug Discovery, [CHIM]Chemical Sciences, Chirality (chemistry), Spectroscopy, Catalysis, Analytical Chemistry
Abstract: International audience; , was a great success with the participation of 340 scientists from 28 countries. The symposium started with two short courses given by four renown professors on "Chiroptical Spectroscopy Methods for Structural Analysis of Chiral Molecules" (G. Longhi and P. Polavarapu) and "Materials" (A. Palmans and G. Markovich). During the following 3 days, we had wonderful invited Plenary and Keynote lectures for which 40% were women lecturers, as well as 58 oral lectures and two poster sessions (162 posters). Very lively discussions and exchanges between the researchers were also observed. We were very happy to have Prof. Larry Nafie who received the Chirality Medal for his seminal contributions to the development and application of vibrational optical activity (VOA). This year, we also had special presentations on "Enantioseparations" honoring some of the founders of the Chirality conferences. We are extremely grateful to the generous academic and industrial sponsors and to the local organizing committee without whom this event would not have been possible. During the symposium, with the great participations from BioTools, Organic Biomolecular Chemistry Journal, INITIO European project, and Association Française de Cristallographie, six poster prizes have been awarded to the following PhD students and post-doctorants: Hinako Okutsu
Published: 2020
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43. Novel self-replicating α-synuclein polymorphs that escape ThT monitoring can spontaneously emerge and acutely spread in neurons

Author: De Giorgi, Francesca, Laferrière, Florent, Zinghirino, Federica, Faggiani, Emilie, Lends, Alons, Bertoni, Mathilde, Yu, Xuan, Grélard, Axelle, Morvan, Estelle, Habenstein, Birgit, Dutheil, Nathalie, Doudnikoff, Evelyne, Daniel, Jonathan, Claverol, Stéphane, Qin, Chuan, Loquet, Antoine, Bezard, Erwan, Ichas, François, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], Université de Bordeaux (UB), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Laferriere, Florent
Subjects: Neurons, Amyloid, MESH: Multiple System Atrophy, Synucleinopathies, animal diseases, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, SciAdv r-articles, Diseases and Disorders, macromolecular substances, nervous system diseases, Mice, nervous system, Cellular Neuroscience, mental disorders, MESH: alpha-Synuclein, alpha-Synuclein, Animals, Benzothiazoles, Research Articles, MESH: Parkinson Disease, Research Article
Abstract: Stealth α-synuclein amyloids proliferate in preparations of preformed fibrils and form aggressive self-replicating strains., The conformational strain diversity characterizing α-synuclein (α-syn) amyloid fibrils is thought to determine the different clinical presentations of neurodegenerative diseases underpinned by a synucleinopathy. Experimentally, various α-syn fibril polymorphs have been obtained from distinct fibrillization conditions by altering the medium constituents and were selected by amyloid monitoring using the probe thioflavin T (ThT). We report that, concurrent with classical ThT-positive products, fibrillization in saline also gives rise to polymorphs invisible to ThT (τ−). The generation of τ− fibril polymorphs is stochastic and can skew the apparent fibrillization kinetics revealed by ThT. Their emergence has thus been ignored so far or mistaken for fibrillization inhibitions/failures. They present a yet undescribed atomic organization and show an exacerbated propensity toward self-replication in cortical neurons, and in living mice, their injection into the substantia nigra pars compacta triggers a synucleinopathy that spreads toward the dorsal striatum, the nucleus accumbens, and the insular cortex.
Published: 2020
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44. Structure and Multitasking of the c-di-GMP-Sensing Cellulose Secretion Regulator BcsE

Author: Samira Zouhir, Meryem Caleechurn, Wiem Abidi, Petya V. Krasteva, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Biologie Structurale des Biofilms (SBB), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Molecular Biology and Physiology, Microbiology, 03 medical and health sciences, Virology, Escherichia coli, Inner membrane, structural biology, Secretion, Cellulose, Cyclic GMP, 030304 developmental biology, 0303 health sciences, ATP synthase, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Escherichia coli Proteins, 030302 biochemistry & molecular biology, Gene Expression Regulation, Bacterial, biochemical phenomena, metabolism, and nutrition, Editor's Pick, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, QR1-502, 3. Good health, Cell biology, Transcription antitermination, Structural biology, c-di-GMP signaling, Biofilms, Porin, biology.protein, biofilm formation, bacteria, cellulose secretion, Diguanylate cyclase, Phosphorus-Oxygen Lyases, Bacterial outer membrane, Research Article
Abstract: Bacterial cellulose is a widespread biofilm component that can modulate microbial fitness and virulence both in the environment and infected hosts. Whereas its secretion generally involves an inner membrane c-di-GMP-dependent synthase tandem (BcsAB) across the bacterial domain of life, enterobacteria feature sophisticated Escherichia coli-like Bcs secretion systems, where multiple additional subunits are either required for secretion or contribute to the maximal production of the polysaccharide in vivo. Here, we demonstrate that essential-for-secretion BcsR and BcsQ regulate each other's folding and stability and are recruited to the inner membrane via c-di-GMP-sensing BcsE and its intraoperon partner, BcsF. Crystallographic and functional data reveal that BcsE features unexpected domain architecture and likely acts on multiple levels to fine-tune bacterial cellulose production, from the early stages of secretion system assembly to the maintenence of a membrane-proximal pool of dimeric c-di-GMP for processive synthase activation., Most bacteria respond to surfaces by biogenesis of intracellular c-di-GMP, which inhibits motility and induces secretion of biofilm-promoting adherence factors. Bacterial cellulose is a widespread biofilm component whose secretion in Gram-negative species requires an inner membrane, c-di-GMP-dependent synthase tandem (BcsAB), an outer membrane porin (BcsC), and various accessory subunits that regulate synthase assembly and function as well as the exopolysaccharide’s chemical composition and mechanical properties. We recently showed that in Escherichia coli, most Bcs proteins form a megadalton-sized secretory nanomachine, but the role and structure of individual regulatory components remained enigmatic. Here, we demonstrate that essential-for-secretion BcsR and BcsQ regulate each other’s folding and stability and are recruited to the inner membrane via c-di-GMP-sensing BcsE and its intraoperon partner BcsF. Crystallographic and solution-based data show that BcsE’s predicted GIL domain is a degenerate receiver-GGDEF domain tandem (BcsEREC*-GGDEF*), where the divergent diguanylate cyclase module binds both dimeric c-di-GMP and BcsQ through mutually independent interfaces. In addition, we reveal that a third N-terminal domain (BcsENTD) determines the protein’s homooligomerization and targeting of BcsERQ to the membrane as well as previously unreported interactions with transcription antitermination complex components. Together, the data suggest that BcsE acts on multiple levels to fine-tune bacterial cellulose secretion, from the early stages of secretion system assembly to the maintenance of a membrane-proximal pool of dimeric c-di-GMP for processive synthase activation.
Published: 2020
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45. Tuning the Chiroptical Properties of Elongated Nano-objects via Hierarchical Organization

Author: Alain Carvalho, Vincent Lemaire, Wenbing Wu, Thierry Buffeteau, Reiko Oda, Jie Gao, Emilie Pouget, Sylvain Nlate, Matthias Pauly, Yann Battie, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Sadron (ICS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes (LCP-A2MC), Université de Lorraine (UL), Buffeteau, Thierry, École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Univ Bordeaux, CNRS UMR 5248, Inst Chim & Biol Membranes & Nanoobjets, INP Bordeaux, Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA), and Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Materials science, Thin films, Aucun, General Physics and Astronomy, Nanoparticle, Physics::Optics, Nanotechnology, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Nano, General Materials Science, Mueller calculus, Thin film, [PHYS.COND]Physics [physics]/Condensed Matter [cond-mat], Chirality, ComputingMilieux_MISCELLANEOUS, Plasmonic nanoparticles, [CHIM.MATE] Chemical Sciences/Material chemistry, Optical properties, business.industry, General Engineering, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Template, Colloidal gold, Nanoparticles, Photonics, 0210 nano-technology, business, Layers
Abstract: International audience; Chiral materials appear as excellent candidates to control and manipulate the polarization of light in optical devices. In nano-photonics, the self-assembly of colloidal plasmonic nanoparticles gives rise to strong resonances in the visible range and, when such organizations are chiral, strong chiroplasmonic effect can be observed. In the present work, we describe the optical properties of chiral artificial nano-photonic materials, Goldhelices, which are hierarchically organized by Grazing Incidence Spraying. These Goldhelices are made by plasmonic nanoparticles (gold) grafted onto helical templates made from silica nanohelices. A comparison of oriented vs non-oriented surfaces has been performed by Mueller matrix polarimetry, showing the importance of the organization of the Goldhelices regarding their interaction with light. Moreover, mono-vs multi-layers photonic films are created and the measured optical properties are discussed and compared to simulations.
Published: 2020
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46. The unprecedented membrane deformation of the human nuclear envelope, in a magnetic field, indicates formation of nuclear membrane invaginations

Author: Anthony Bouter, Christopher J. Applebee, Regine Dazzoni, Banafshé Larijani, Antoine Loquet, Erick J. Dufourc, Estelle Morvan, Axelle Grélard, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Bath [Bath], The IdEx University of Bordeaux and the Euskampus are thanked for providing funding towards a PhD thesis to RD. The Fundacion de Biofisika for co-funding the RD’s PhD. Elkartek Grant (RVCTI) Omega Oceanomics awarded to BL. Finacial support to BL included Department of Education, Basque Government (IT1270-19), Spanish Ministry Grant (MINECO) PROJECTS of EXCELLENCE (BFU2015-65625-P. Financial support from the TGIR-RMN-THC FR3050 CNRS for conducting the research is gratefully acknowledged. This work benefited from the facilities and expertise of the Biophysical and Structural Chemistry platform at IECB, CNRS UMS3033, INSERM US001, Bordeaux University, France., Bodescot, Myriam, Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, 030103 biophysics, Magnetic Resonance Spectroscopy, Membrane Fluidity, Nuclear Envelope, Biophysics, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, lcsh:Medicine, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Kidney, Phosphatidylinositols, Phase Transition, Article, Membrane bending, 03 medical and health sciences, chemistry.chemical_compound, Membrane Lipids, Membrane biophysics, Organelle, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Humans, Lamellar structure, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Nuclear membrane, lcsh:Science, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Unsaturated fatty acid, Phospholipids, Multidisciplinary, Cholesterol, lcsh:R, Cell Membrane, Membrane structure and assembly, Nuclear magnetic resonance spectroscopy, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 030104 developmental biology, Membrane, medicine.anatomical_structure, Magnetic Fields, chemistry, Fatty Acids, Unsaturated, lcsh:Q
Abstract: Human nuclear membrane (hNM) invaginations are thought to be crucial in fusion, fission and remodeling of cells and present in many human diseases. There is however little knowledge, if any, about their lipid composition and dynamics. We therefore isolated nuclear envelope lipids from human kidney cells, analyzed their composition and determined the membrane dynamics after resuspension in buffer. The hNM lipid extract was composed of a complex mixture of phospholipids, with high amounts of phosphatidylcholines, phosphatidylinositols (PI) and cholesterol. hNM dynamics was determined by solid-state NMR and revealed that the lamellar gel-to-fluid phase transition occurs below 0 °C, reflecting the presence of elevated amounts of unsaturated fatty acid chains. Fluidity was higher than the plasma membrane, illustrating the dual action of Cholesterol (ordering) and PI lipids (disordering). The most striking result was the large magnetic field-induced membrane deformation allowing to determine the membrane bending elasticity, a property related to hydrodynamics of cells and organelles. Human Nuclear Lipid Membranes were at least two orders of magnitude more elastic than the classical plasma membrane suggesting a physical explanation for the formation of nuclear membrane invaginations.
Published: 2019
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47. CD63-GPC1-Positive Exosomes Coupled with CA19-9 Offer Good Diagnostic Potential for Resectable Pancreatic Ductal Adenocarcinoma

Author: Aurélie Bedel, Camille Buscail, O Degrandi, Laurence Chiche, Christophe Laurent, Charline Caumont, Séverine Verdon, Alain Brisson, Alexandre Chauvet, François Moreau-Gaudry, Véronique Vendrely, Marion Marty, Pascaline Quincy, Isabelle Lamrissi, Etienne Buscail, Isabelle Moranvillier, Sandrine Dabernat, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université de Bordeaux (UB), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Patrick Brou de Lauriere Fondation, Celgene company, Groupement Interregional de Recherche Clinique et d'Innovation Sud-Ouest OutreMer (GIRCI-SOOM), Admin, Oskar, AUDOUX, Michèle, Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Inserm U1035, Biotherapies des Maladies Genetiques et Cancers, Univ Bordeaux, CHU de Bordeaux, Pole de Biologie et Pathologie, and Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Original article, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Exosome, Gastroenterology, lcsh:RC254-282, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Medicine, Liquid biopsy, Prospective cohort study, [CHIM.MATE] Chemical Sciences/Material chemistry, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, CD63, business.industry, Cancer, [CHIM.MATE]Chemical Sciences/Material chemistry, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Microvesicles, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, CA19-9, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Tumor-released extracellular vesicles (EVs) contain tumor-specific cargo distinguishing them from healthy EVs, and making them eligible as circulating biomarkers. Glypican 1 (GPC1)-positive exosome relevance as liquid biopsy elements is still debated. We carried out a prospective study to quantify GPC1-positive exosomes in sera from pancreatic ductal adenocarcinoma (PDAC) patients undergoing up-front surgery, as compared to controls including patients without cancer history and patients displaying pancreatic preneoplasic lesions. Sera were enriched in EVs, and exosomes were pulled down with anti-CD63 coupled magnetic beads. GPC1-positive bead percentages determined by flow cytometry were significantly higher in PDAC than in the control group. Diagnosis accuracy reached 78% (sensitivity 64% and specificity 90%), when results from peripheral and portal blood were combined. In association with echo-guided-ultrasound-fine-needle-aspiration (EUS-FNA) negative predictive value was 80% as compared to 33% for EUS-FNA only. This approach is clinically relevant as a companion test to the already available diagnostic tools, since patients with GPC1-positive exosomes in peripheral blood showed decreased tumor free survival.
Published: 2019
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48. Nanodomain Clustering of the Plant Protein Remorin by Solid-State NMR

Author: Anthony Legrand, Denis Martinez, Axelle Grélard, Melanie Berbon, Estelle Morvan, Arpita Tawani, Antoine Loquet, Sébastien Mongrand, Birgit Habenstein, Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Research Council, ANR-16-CE20-0008,PotyMove,Facteurs cellulaires recrutés par les potyvirus pour leur transport intercellulaire : de nouvelles sources de résistance des plantes?(2016), Mongrand, Sébastien, Facteurs cellulaires recrutés par les potyvirus pour leur transport intercellulaire : de nouvelles sources de résistance des plantes? - - PotyMove2016 - ANR-16-CE20-0008 - AAPG2016 - VALID, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Soutien à la Recherche de l'Institut Européen de Chimie Biologique, Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Européen de Chimie et de Biologie-Université Sciences et Technologies - Bordeaux 1-Institut de Chimie du CNRS (INC)
Subjects: 0301 basic medicine, Deuterium NMR, Thermotropism, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, nanodomains, 03 medical and health sciences, 0302 clinical medicine, sterol, plant protein, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biosciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, membrane protein, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, Lipid raft, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], lcsh:QH301-705.5, Original Research, remorin, [CHIM.MATE] Chemical Sciences/Material chemistry, Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, lipid raft, phosphoinositide, 030104 developmental biology, Order (biology), Membrane, Membrane protein, Solid-state nuclear magnetic resonance, lcsh:Biology (General), Plant protein, 030220 oncology & carcinogenesis, Biophysics, solid-state NMR, lipids (amino acids, peptides, and proteins)
Abstract: Nanodomains are dynamic membrane subcompartments, enriched in specific lipid, and protein components that act as functional platforms to manage an abundance of cellular processes. The remorin protein of plants is a well-established nanodomain marker and widely serves as a paradigm to study nanodomain clustering. Located at the inner leaflet of the plasma membrane, remorins perform essential functions during signaling. Using deuterium and phosphorus solid-state NMR, we inquire on the molecular determinants of the lipid-protein and protein-protein interactions driving nanodomain clustering. By monitoring thermotropism properties, lipid acyl chain order and membrane thickness, we report the effects of phosphoinositides and sterols on the interaction of various remorin peptides and protein constructs with the membrane. We probed several critical residues involved in this interaction and the involvement of the coiled-coil homo-oligomerisation domain into the formation of remorin nanodomains. We trace the essential role of the pH in nanodomain clustering based on anionic lipids such as phosphoinositides. Our results reveal a complex interplay between specific remorin residues and domains, the environmental pH and their resulting effects on the lipid dynamics for phosphoinositide-enriched membranes., Les nanodomaines sont des sous-compartiments membranaires dynamiques, enrichis en lipides spécifiques et en composants protéiques qui servent de plateformes fonctionnelles pour gérer une abondance de processus cellulaires. La protéine remorine des plantes est un marqueur de nanodomaines bien établi et sert largement de paradigme pour l'étude des grappes de nanodomaines. Situés au niveau de la foliole interne de la membrane plasmique, les remorines remplissent des fonctions essentielles lors de la signalisation. En utilisant la RMN à l'état solide du deutérium et du phosphore, nous étudions les déterminants moléculaires des interactions lipide-protéine et protéine-protéine à l'origine des amas de nanodomaines. En surveillant les propriétés du thermotropisme, l'ordre de la chaîne acyle lipidique et l'épaisseur de la membrane, nous rapportons les effets des phosphoinositides et des stérols sur l'interaction de divers peptides et constructions protéiques de remorine avec la membrane. Nous avons étudié plusieurs résidus critiques impliqués dans cette interaction et l'implication du domaine de l'homo-oligomérisation à bobine enroulée dans la formation des nanodomaines remoriniques. Nous retraçons le rôle essentiel du pH dans la formation de grappes de nanodomaines à base de lipides anioniques tels que les phosphoinositides. Nos résultats révèlent une interaction complexe entre les résidus et les domaines spécifiques des remorines, le pH environnemental et leurs effets sur la dynamique lipidique des membranes enrichies en phosphoinositides.
Published: 2019
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49. Ionpair-π interactions favor cell penetration of arginine/tryptophan-rich cell-penetrating peptides

Author: Astrid Walrant, Natpasit Chaianantakul, Isabel D. Alves, Françoise Illien, Antonio Frontera, Sandrine Sagan, Sophie Lecomte, Sébastien Cardon, Manjula Pallerla, Claudia Girardet, Antonio Bauzá, Fabienne Burlina, University of Cambridge [UK] (CAM), Departament de Quimica, Universitat des Illes Balears, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche Moléculaire sur les Antibiotiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universitat de les Illes Balears (UIB), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Naresuan University, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie Moléculaire de Paris Centre (FR 2769), Université Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: 0301 basic medicine, Chinese Hamster Ovary, Isothermal Titration Calorimetry, Arginine, CHO, [SDV]Life Sciences [q-bio], POPG, Peptide, Cell-Penetrating Peptides, Attenuated Total Reflection Fourier Transformed Infra Red, 01 natural sciences, Biochemistry, DFT, DSC, Cell membrane, Cricetinae, Lipid membrane, Lipid bilayer, Internalization, Glycosaminoglycans, media_common, Cell-penetrating-peptide, chemistry.chemical_classification, GAG, 0303 health sciences, cell-penetrating-peptide / ionpair-pi interaction / glycosaminoglycan / lipid membrane / tryptophan / arginine Abbreviations ART-FTIR, Differential Scanning Calorimetry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Tryptophan, [CHIM.MATE]Chemical Sciences/Material chemistry, Endocytosis, Protein Transport, Membrane, medicine.anatomical_structure, Thermodynamics, DMPG, media_common.quotation_subject, 1-palmitoyl-2, Biophysics, CHO Cells, 010402 general chemistry, Cell-Penetrating Peptide, 03 medical and health sciences, Cricetulus, medicine, Animals, Humans, Amino Acid Sequence, 030304 developmental biology, Ionpair-pi interaction, Cell Membrane, Isothermal titration calorimetry, Cell Biology, ITC, 0104 chemical sciences, 030104 developmental biology, Glycosaminoglycan, Cell-penetrating peptide, Density functional theory, CPP, 2-dimyristoyl sn-glycero-3-phospho-(1'-rac- glycerol)
Abstract: Cell-penetrating peptides (CPPs) internalization can occur both by endocytosis and direct translocation through the cell membrane. These different entry routes suggest that molecular partners at the plasma membrane, phospholipids or glycosaminoglycans (GAGs), bind CPPs with different affinity or selectivity. The analysis of sequence-dependent interactions of CPPs with lipids and GAGs should lead to a better understanding of the molecular mechanisms underlying their internalization. CPPs are short sequences generally containing a high number of basic arginines and lysines and sometimes aromatic residues, in particular tryptophans. Tryptophans are crucial residues in membrane-active peptides, because they are important for membrane interaction. Membrane-active peptides often present facial amphiphilicity, which also promote the interaction with lipid bilayers. To study the role of Trp and facial amphiphilicity in cell interaction and penetration of CPPs, a nonapeptide series containing only Arg, Trp or D-Trp residues at different positions was designed. Our quantitative study indicates that to maintain/increase the uptake efficiency, Arg can be advantageously replaced by Trp in the nonapeptides. The presence of Trp in oligoarginines increases the uptake in cells expressing GAGs at their surface, when it only compensates for the loss of Arg and maintains similar peptide uptake in GAG-deficient cells. In addition, we show that facial amphiphilicity is not required for efficient uptake of these nonapeptides. Thermodynamic analyses point towards a key role of Trp that highly contributes to the binding enthalpy of complexes formation. Density functional theory (DFT) analysis highlights that salt bridge-π interactions play a crucial role for the GAG-dependent entry mechanisms.
Published: 2019
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50. itms

Author: Jobin, Marie-Lise, Vamparys, Lydie, Deniau, Romain, Grélard, Axelle, Mackereth, Cameron, Fuchs, Patrick, Alves, Isabel, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bioinformatique génomique et moléculaire ((U 726)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Laboratoire des biomolécules (LBM UMR 7203), Institut National de la Santé et de la Recherche Médicale (INSERM)-Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Alves, Isabel
Subjects: [CHIM.MATE] Chemical Sciences/Material chemistry, peptide–lipid interaction, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [CHIM.MATE]Chemical Sciences/Material chemistry, molecular dynamics, NMR, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, lcsh:Chemistry, lipid model systems, lcsh:Biology (General), lcsh:QD1-999, peptide-lipid interaction, membrane biophysics, lcsh:QH301-705.5, cell-penetrating peptide
Abstract: International audience; Cell-penetrating peptides (CPPs) are short peptides that can translocate and transport cargoes into the intracellular milieu by crossing biological membranes. The mode of interaction and internalization of cell-penetrating peptides has long been controversial. While their interaction with anionic membranes is quite well understood, the insertion and behavior of CPPs in zwitterionic membranes, a major lipid component of eukaryotic cell membranes, is poorly studied. Herein, we investigated the membrane insertion of RW16 into zwitterionic membranes, a versatile CPP that also presents antibacterial and antitumor activities. Using complementary approaches, including NMR spectroscopy, fluorescence spectroscopy, circular dichroism, and molecular dynamic simulations, we determined the high-resolution structure of RW16 and measured its membrane insertion and orientation properties into zwitterionic membranes. Altogether, these results contribute to explaining the versatile properties of this peptide toward zwitterionic lipids.
Published: 2019
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