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9 results on '"Aurélien Thureau"'

1. The structure of pathogenic huntingtin exon 1 defines the bases of its aggregation propensity

Author

Carlos A. Elena-Real, Amin Sagar, Annika Urbanek, Matija Popovic, Anna Morató, Alejandro Estaña, Aurélie Fournet, Christine Doucet, Xamuel L. Lund, Zhen-Dan Shi, Luca Costa, Aurélien Thureau, Frédéric Allemand, Rolf E. Swenson, Pierre-Emmanuel Milhiet, Ramon Crehuet, Alessandro Barducci, Juan Cortés, Davy Sinnaeve, Nathalie Sibille, Pau Bernadó, Centre de Biologie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Équipe Robotique et InteractionS (LAAS-RIS), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Institut Laue-Langevin (ILL), National Institutes of Health [Bethesda] (NIH), Beamline SWING, Synchrotron SOLEIL, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Institute for Advanced Chemistry of Catalonia, Biologie Structurale Intégrative (ERL 9002 - BSI ), 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 National de la Recherche Scientifique (CNRS), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), ANR-10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), ANR-17-CE11-0022,GPCteR,Mécanismes moléculaires des régions C-terminales désordonnées et fonctionnelles des RCPG et impact sur les voies de la signalisation cellulaire dépendantes de l'arrestine(2017), ANR-19-P3IA-0004,ANITI,Artificial and Natural Intelligence Toulouse Institute(2019), European Project: 648030,H2020,ERC-2014-CoG,chemREPEAT(2015), and European Commission

Subjects
Huntington’s disease is a neurodegenerative disorder, poly-Q-related diseases, Pathogenic huntingtin, Structural Biology, [SDV]Life Sciences [q-bio], Proteins, Protein aggregation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], HTT gene, Solution-state NMR, Molecular Biology
Abstract

Huntington's disease is a neurodegenerative disorder caused by a CAG expansion in the first exon of the HTT gene, resulting in an extended polyglutamine (poly-Q) tract in huntingtin (httex1). The structural changes occurring to the poly-Q when increasing its length remain poorly understood due to its intrinsic flexibility and the strong compositional bias. The systematic application of site-specific isotopic labeling has enabled residue-specific NMR investigations of the poly-Q tract of pathogenic httex1 variants with 46 and 66 consecutive glutamines. Integrative data analysis reveals that the poly-Q tract adopts long α-helical conformations propagated and stabilized by glutamine side chain to backbone hydrogen bonds. We show that α-helical stability is a stronger signature in defining aggregation kinetics and the structure of the resulting fibrils than the number of glutamines. Our observations provide a structural perspective of the pathogenicity of expanded httex1 and pave the way to a deeper understanding of poly-Q-related diseases., We thank G. Otting (Australian National University, Canberra, Australia) for providing the BL21 (DE3) Star::RF1-CBD3 strain. This work was supported by the European Research Council under the European Union’s H2020 Framework Programme (2014–2020)/ERC grant agreement no. 648030 and Labex EpiGenMed, an Investissements d’avenir program (grant no. ANR-10-LABX-12-01) awarded to P.B., grant no. ANR-17-CE11-0022-01 awarded to N.S. and grant no. ANR-19-PI3A-0004 awarded to J.C. The Centre for Structural Biology (CBS) is a member of France-BioImaging (FBI) and the French Infrastructure for Integrated Structural Biology, two national infrastructures supported by the French National Research Agency (grant nos. ANR-10-INBS-04-01 and ANR-10-INBS-05, respectively). A.U. is supported by a grant from the Fondation pour la Recherche Médicale (grant no. SPF20150934061). D.S. acknowledges a grant from the Métropole Européenne de Lille (PUSHUP). G. Levy (Université de Lille) is thanked for help with sample preparation and the 19F-NMR experiments. This work benefited from the high-performance computing resources of CSUC and the CALMIP supercomputing center under the allocations 2016-P16032 and 2021-P21043. The 600 MHz spectrometer for 19F-NMR measurements is funded by the Nord Region Council, CNRS, Institut Pasteur de Lille, the European Community (European Regional Development Fund, ERDF), the French Ministry of Research and the Université de Lille and by the CTRL CPER cofunded by the European Union with the ERDF, by the Hauts-de-France Regional Council (contract no. 17003781), Métropole Européenne de Lille (contract no. 2016_ESR_05) and the French State (contract no .2017-R3-CTRL-Phase1). We thank the SWING beamline at the SOLEIL synchrotron, Saint-Aubin, France (proposal 20181386), and P12 beamline at PETRAIII, Hamburg, Germany, for beamtime allocation to the project and assistance during data collection.

Published
2023

2. Medical contrast agents as promising tools for biomacromolecular SAXS experiments

Author

Frank Gabel, Sylvain Engilberge, Emmanuelle Schmitt, Aurélien Thureau, Yves Mechulam, Javier Pérez, Eric Girard, 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), Laboratoire de Biologie Structurale de la Cellule (BIOC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), ANR-13-BS07-0007,Ln23,Complexes de lanthanide comme nouveaux chevaux de Troie pour la détermination structurale de protéines(2013), and ANR-21-CE11-0025,DeepSAXS,Variation profonde de contraste SAXS : un nouvel outil pour la biologie structurale(2021)

Subjects
tools for SAXS, Iohexol, Gd-HPDO3A, Contrast Media, Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, SAXS, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Lanthanoid Series Elements, small-angle scattering, X-Ray Diffraction, Structural Biology, medical contrast agents, Scattering, Small Angle, contrast variation, Solvents, RNA, macromolecular complexes, electron density
Abstract

Small-angle X-ray scattering (SAXS) has become an indispensable tool in structural biology, complementing atomic-resolution techniques. It is sensitive to the electron-density difference between solubilized biomacromolecules and the buffer, and provides information on molecular masses, particle dimensions and interactions, low-resolution conformations and pair distance-distribution functions. When SAXS data are recorded at multiple contrasts, i.e. at different solvent electron densities, it is possible to probe, in addition to their overall shape, the internal electron-density profile of biomacromolecular assemblies. Unfortunately, contrast-variation SAXS has been limited by the range of solvent electron densities attainable using conventional co-solutes (for example sugars, glycerol and salt) and by the fact that some biological systems are destabilized in their presence. Here, SAXS contrast data from an oligomeric protein and a protein–RNA complex are presented in the presence of iohexol and Gd-HPDO3A, two electron-rich molecules that are used in biomedical imaging and that belong to the families of iodinated and lanthanide-based complexes, respectively. Moderate concentrations of both molecules allowed solvent electron densities matching those of proteins to be attained. While iohexol yielded higher solvent electron densities (per mole), it interacted specifically with the oligomeric protein and precipitated the protein–RNA complex. Gd-HPDO3A, while less efficient (per mole), did not disrupt the structural integrity of either system, and atomic models could be compared with the SAXS data. Due to their elevated solubility and electron density, their chemical inertness, as well as the possibility of altering their physico-chemical properties, lanthanide-based complexes represent a class of molecules with promising potential for contrast-variation SAXS experiments on diverse biomacromolecular systems.

Published
2022

3. Overall Structures of Mycobacterium tuberculosis DNA Gyrase Reveal the Role of a Corynebacteriales GyrB-Specific Insert in ATPase Activity

Author

Claudine Mayer, Pedro M. Alzari, Clément Giffard, Aurélien Thureau, Stéphanie Petrella, Françoise Bonneté, Alexandra Aubry, Estelle Capton, Bertrand Raynal, CCSD, Accord Elsevier, Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Biophysique Moléculaire (Plate-forme), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie physico-chimique des protéines membranaires (LBPC-PM (UMR_7099)), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was funded by Institut Pasteur, Université Paris Diderot, and Sorbonne-Université (France)., Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
type IIA topoisomerases, Models, Molecular, Protein Conformation, alpha-Helical, ATPase, Gene Expression, Crystallography, X-Ray, ATPase activity, DNA gyrase, Adenosine Triphosphate, Structural Biology, Cloning, Molecular, Adenosine Triphosphatases, molecular machine, 0303 health sciences, biology, Chemistry, Drug discovery, 030302 biochemistry & molecular biology, Molecular machine, Recombinant Proteins, 3. Good health, Biochemistry, DNA Gyrase, Protein Binding, Adenylyl Imidodiphosphate, Genetic Vectors, DNA-binding protein, Corynebacterium, fluoroquinolone, Cleavage (embryo), [PHYS.PHYS.PHYS-CHEM-PH] Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Mycobacterium tuberculosis, Corynebacteriales, 03 medical and health sciences, Escherichia coli, Atpase activity, Protein Interaction Domains and Motifs, Amino Acid Sequence, Protein Structure, Quaternary, SAXS experiments, Molecular Biology, 030304 developmental biology, Binding Sites, Sequence Homology, Amino Acid, DNA, biology.organism_classification, Kinetics, biology.protein, Protein Conformation, beta-Strand, X-ray structure, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Apoproteins, Sequence Alignment
Abstract

International audience; Despite sharing common features, previous studies have shown that gyrases from different species have been modified throughout evolution to modulate their properties. Here, we report two crystal structures of Mycobacterium tuberculosis DNA gyrase, an apo and AMPPNP-bound form at 2.6-Å and 3.3-Å resolution, respectively. These structures provide high-resolution structural data on the quaternary organization and interdomain connections of a gyrase (full-length GyrB-GyrA57)2 thus providing crucial inputs on this essential drug target. Together with small-angle X-ray scattering studies, they revealed an "extremely open" N-gate state, which persists even in the DNA-free gyrase-AMPPNP complex and an unexpected connection between the ATPase and cleavage core domains mediated by two Corynebacteriales-specific motifs, respectively the C-loop and DEEE-loop. We show that the C-loop participates in the stabilization of this open conformation, explaining why this gyrase has a lower ATPase activity. Our results image a conformational state which might be targeted for drug discovery.

Published
2018

4. A Brief Survey of State-of-the-Art BioSAXS

Author

Pierre Roblina, Patrice Vachette, Javier Pérez, Aurélien Thureau, Thomas Bizien, Dominique Durand, Communication, information, médias (Paris), Unité Mixte de Recherches sur les Herbivores ( UMR 1213 Herbivores ), VetAgro Sup ( VAS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique ( INRA ), SAD Paysage ( SAD Paysage ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), SWING beamline, Biophysics Group ( SWING ), Synchrotron SOLEIL, 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 National de la Recherche Agronomique (INRA), SWING beamline, Biophysics Group (SWING), Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), SAD Paysage (SAD Paysage), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay

Subjects
Models, Molecular, 0301 basic medicine, Beamline, conformation, Macromolecular Substances, [SDV]Life Sciences [q-bio], Nanotechnology, Biology, Biochemistry, Field (computer science), 03 medical and health sciences, X-Ray Diffraction, Structural Biology, Scattering, Small Angle, Instrumentation (computer programming), structure, solution, Structure (mathematical logic), Molecular Structure, [ SDV ] Life Sciences [q-bio], small-angle X-ray Scattering, Macromolecular crystallography, Computational Biology, General Medicine, Data science, Optical quality, hybrid methods, 030104 developmental biology, biological macromolecules, State (computer science), Software, Synchrotrons
Abstract

International audience; In the field of structural biology, Small Angle X-ray Scattering (SAXS) has undergone a tremendous evolution in the last two decades. From a craft reserved to a few experts in the late 80's, it has now turned into a high-throughput technique, following the same trend as macromolecular crystallography. Synchrotron radiation has played a key role in this evolution, by providing intense X-ray beams of high optical quality that made possible the recording of statistically meaningful data from weakly scattering biological solutions in a reasonable time. This, in turn, prompted the development of powerful and specific software for data analysis and modeling. In this mini-review, mainly addressed towards a broad readership, representing as many potential users, we try to summarize the latest aspects of evolution of BioSAXS, both conceptually and from the point of view of instrumentation. We emphasize the need for complementary experimental or computational techniques used in combination with SAXS. The great potential of these multi-pronged approaches is illustrated by a series of very recent studies covering the various ways and means of using BioSAXS.

Published
2016

5. Hybrid Structural Analysis of the Arp2/3 Regulator Arpin Identifies Its Acidic Tail as a Primary Binding Epitope

Author

Susan Fetics, Jacqueline Cherfils, Irene Dang, Valérie Campanacci, Javier Pérez, Magali Aumont-Nicaise, Aurélien Thureau, Alexis Gautreau, 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), Biochimie Structurale des Microtubules, des Kinésines et de leurs Cargos (MIKICA), 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), Mesures d'interactions protéine-protéine (PIM), and Département Plateforme (PF I2BC)

Subjects
0301 basic medicine, Small Angle, Fish Proteins, Models, Molecular, Protein Conformation, [SDV]Life Sciences [q-bio], Cell leading edge, Plasma protein binding, macromolecular substances, Biology, Crystallography, X-Ray, Epitope, Actin-Related Protein 2-3 Complex, Scattering, 03 medical and health sciences, Epitopes, 0302 clinical medicine, Protein structure, X-Ray Diffraction, Models, Structural Biology, Scattering, Small Angle, Animals, Humans, Binding site, Molecular Biology, Actin, Crystallography, Binding Sites, Fishes, Molecular, 030104 developmental biology, Biochemistry, Biophysics, X-Ray, Ankyrin repeat, Carrier Proteins, 030217 neurology & neurosurgery, Protein Binding
Abstract

SummaryArpin is a newly discovered regulator of actin polymerization at the cell leading edge, which steers cell migration by exerting a negative control on the Arp2/3 complex. Arpin proteins have an acidic tail homologous to the acidic motif of the VCA domain of nucleation-promoting factors (NPFs). This tail is predicted to compete with the VCA of NPFs for binding to the Arp2/3 complex, thereby mitigating activation and/or tethering of the complex to sites of actin branching. Here, we investigated the structure of full-length Arpin using synchrotron small-angle X-ray scattering, and of its acidic tail in complex with an ankyrin repeats domain using X-ray crystallography. The data were combined in a hybrid model in which the acidic tail extends from the globular core as a linear peptide and forms a primary epitope that is readily accessible in unbound Arpin and suffices to tether Arpin to interacting proteins with high affinity.

Published
2015

6. SAXS and X-ray crystallography suggest an unfolding model for the GDP/GTP conformational switch of the small GTPase Arf6

Author

Mahel Zeghouf, Valérie Biou, Kaheina Aizel, Carine van Heijenoort, Eric Jacquet, Javier Pérez, Sebastian Hansson, Pierre Roblin, Eric Guittet, Aurélien Thureau, Jacqueline Cherfils, Bernard Guibert, Institut de Chimie des Substances Naturelles (ICSN), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Protein Folding, Protein Conformation, Protein Data Bank (RCSB PDB), GTPase, Crystallography, X-Ray, Guanosine Diphosphate, 03 medical and health sciences, chemistry.chemical_compound, Protein structure, X-Ray Diffraction, Structural Biology, Scattering, Small Angle, Humans, Small GTPase, Molecular Biology, 030304 developmental biology, 0303 health sciences, ADP-Ribosylation Factors, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 030302 biochemistry & molecular biology, Crystallography, chemistry, ADP-Ribosylation Factor 6, Guanosine diphosphate, Thermodynamics, Protein folding, Guanosine Triphosphate, Guanine nucleotide exchange factor, Heteronuclear single quantum coherence spectroscopy
Abstract

International audience; The small GTPases Arf1 and Arf6 have nonoverlapping functions in cellular traffic despite their very high sequence and structural resemblance. Notably, the exquisite isoform specificity of their guanine nucleotide exchange factors and their distinctive sensitivity to the drug brefeldin A cannot be explained by any straightforward structural model. Here we integrated structural and spectroscopic methods to address this issue using Δ13Arf6-GDP, a truncated mutant that mimics membrane-bound Arf6-GDP. The crystal structure of Δ13Arf6-GDP reveals an unprecedented unfolding of the GTPase core β-strands, which is fully accounted for by small-angle X-ray scattering data in solution and by ab initio three-dimensional envelope calculation. NMR chemical shifts identify this structural disorder in Δ13Arf6-GDP, but not in the closely related Δ17Arf1-GDP, which is consistent with their comparative thermodynamic and hydrodynamic analyses. Taken together, these experiments suggest an unfolding model for the nucleotide switch of Arf6 and shed new light on its biochemical differences with Arf1.

Published
2010

9. Structure and inhibition of Arf GTPases

Author

V. Buosi, Mahel Zeghouf, Jacqueline Cherfils, Aurélien Thureau, Jean-Christophe Zeeh, Eric Guittet, Valérie Biou, and C. van Heijenoort

Subjects
Structural Biology, Chemistry, GTPase, Cell biology
Published
2008

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