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Your search keyword '"Marina Casiraghi"' showing total 6 results
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6 results on '"Marina Casiraghi"'

1. Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor

Author

Laurent J. Catoire, Sonia Cantel, Marjorie Damian, Jean-Alain Fehrentz, Maxime Louet, Antoniel As Gomes, Jean-Louis Banères, Sophie Mary, Paulo R. Batista, David Perahia, Paulo Mascarello Bisch, Mauricio Gs Costa, Khoubaib Ben Haj Salah, Céline M'Kadmi, Marina Casiraghi, Pedro Renault, Severine Denoyelle, Nicolas Floquet, 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), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-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)), 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), Department of Molecular and Cellular Physiology [Stanford], Stanford Medicine, Stanford University-Stanford University, Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Universidade Federal do Rio de Janeiro (UFRJ), This work was supported by CNRS, Université de Montpellier, Agence Nationale de la Recherche (ANR-17-CE11-0011, ANR-17-CE11-22, ANR-17-CE18-0022), EpiGenMed Labex (post-doctoral fellowship to KBH) and DYNAMO Labex (post-doctoral fellowship to MC). This programreceived funding from the European Union’s Horizon 2020 research and innovation programmeunder the Marie Sklodowska-Curie grant agreement n˚ 799376. Mass spectrometry analyses wereperformed on the instruments located in the IBMM platform of instrumentation, Laboratoire deMesures Physiques (LMP) of Université de Montpellier. We thank GENCI (Grand EquipementNational de Calcul Intensif), CINES (Centre Informatique National de l’Enseignement Supérieur), and IDRIS (Institut du développement et des ressources en informatique scientifique) for computational, ANR-17-CE11-0011,allosig,allostérie, dynamique conformationnelle et signalisation via les RCPG(2017), 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), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)

Subjects
QH301-705.5, Science, Growth hormone secretagogue receptor, Chemical biology, chemical biology, 010402 general chemistry, Ligands, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Receptors, G-Protein-Coupled, 03 medical and health sciences, Molecular dynamics, GPCR, Biochemistry and Chemical Biology, biochemistry, Humans, Biology (General), Receptor, Receptors, Ghrelin, 030304 developmental biology, G protein-coupled receptor, chemistry.chemical_classification, 0303 health sciences, General Immunology and Microbiology, [SDV.BA]Life Sciences [q-bio]/Animal biology, General Neuroscience, digestive, oral, and skin physiology, E. coli, General Medicine, Ghrelin, 0104 chemical sciences, Amino acid, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Transmembrane domain, chemistry, Biophysics, Medicine, signaling, hydration, Research Article, Human, Signal Transduction
Abstract

International audience; There is increasing support for water molecules playing a role in signal propagation through G protein-coupled receptors (GPCRs). However, exploration of the hydration features of GPCRs is still in its infancy. Here, we combined site-specific labeling with unnatural amino acids to molecular dynamics to delineate how local hydration of the ghrelin receptor growth hormone secretagogue receptor (GHSR) is rearranged upon activation. We found that GHSR is characterized by a specific hydration pattern that is selectively remodeled by pharmacologically distinct ligands and by the lipid environment. This process is directly related to the concerted movements of the transmembrane domains of the receptor. These results demonstrate that the conformational dynamics of GHSR are tightly coupled to the movements of internal water molecules, further enhancing our understanding of the molecular bases of GPCR-mediated signaling.

Published
2021

2. Author response: Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor

Author

Céline M'Kadmi, Maxime Louet, Paulo R. Batista, Paulo Mascarello Bisch, Sophie Mary, Nicolas Floquet, Marina Casiraghi, Jean-Alain Fehrentz, Khoubaib Ben Haj Salah, Laurent J. Catoire, Sonia Cantel, Jean-Louis Banères, Antoniel As Gomes, David Perahia, Mauricio Gs Costa, Marjorie Damian, Pedro Renault, and Severine Denoyelle

Subjects
Chemistry, Water Movements, Dynamics (mechanics), Biophysics, Ghrelin, G protein-coupled receptor
Published
2021

3. NMR analysis of GPCR conformational landscapes and dynamics

Author

Laurent Catoire, Karine Moncoq, Elodie Point, Jean-Louis Banères, Alexandre Pozza, Marina Casiraghi, Physico-chimie moléculaire des membranes biologiques (PCMMB), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut de biochimie et biophysique moléculaire et cellulaire (IBBMC), Université Paris-Sud - Paris 11 (UP11)-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), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-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), Centre National de la Recherche Scientifique (CNRS), Stanford University, Institut de biologie physico-chimique (IBPC (FR_550)), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)

Subjects
0301 basic medicine, Models, Molecular, Magnetic Resonance Spectroscopy, Protein Conformation, Allosteric regulation, 030209 endocrinology & metabolism, Context (language use), Computational biology, Crystallography, X-Ray, Biochemistry, Receptors, G-Protein-Coupled, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Molecular level, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, ComputingMilieux_MISCELLANEOUS, G protein-coupled receptor, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Mechanism (biology), Cryoelectron Microscopy, Energy landscape, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Structural biology, Function (biology), Protein Binding, Signal Transduction
Abstract

Understanding the signal transduction mechanism mediated by the G Protein-Coupled Receptors (GPCRs) in eukaryote cells represents one of the main issues in modern biology. At the molecular level, various biophysical approaches have provided important insights on the functional plasticity of these complex allosteric machines. In this context, X-ray crystal structures published during the last decade represent a major breakthrough in GPCR structural biology, delivering important information on the activation process of these receptors through the description of the three-dimensional organization of their active and inactive states. In complement to crystals and cryo-electronic microscopy structures, information on the probability of existence of different GPCR conformations and the dynamic barriers separating those structural sub-states is required to better understand GPCR function. Among the panel of techniques available, nuclear magnetic resonance (NMR) spectroscopy represents a powerful tool to characterize both conformational landscapes and dynamics. Here, we will outline the potential of NMR to address such biological questions, and we will illustrate the functional insights that NMR has brought in the field of GPCRs in the recent years.

Published
2018

4. Illuminating the Energy Landscape of GPCRs: The Key Contribution of Solution-State NMR Associated with Escherichia coli as an Expression Host

Author

Jean-Louis Banères, Ewen Lescop, Marina Casiraghi, Marjorie Damian, Laurent Catoire, Stanford University, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Protein Conformation, Solution state, [SDV]Life Sciences [q-bio], Computational biology, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, Receptors, G-Protein-Coupled, 03 medical and health sciences, Protein structure, Escherichia coli, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Nuclear Magnetic Resonance, Biomolecular, ComputingMilieux_MISCELLANEOUS, G protein-coupled receptor, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Host (biology), Eukaryota, Proteins, Energy landscape, 0104 chemical sciences, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 030104 developmental biology, Gene Expression Regulation, Expression (architecture), Isotope Labeling, Function (biology)
Abstract

Conformational dynamics of GPCRs are central to their function but are difficult to explore at the atomic scale. Solution-state NMR has provided the major contribution in that area of study during the past decade, despite nonoptimized labeling schemes due to the use of insect cells and, to a lesser extent, yeast as the main expression hosts. Indeed, the most efficient isotope-labeling scheme ever to address energy landscape issues for large proteins or protein complexes relies on the use of 13CH3 probes immersed in a perdeuterated dipolar environment, which is essentially out of reach of eukaryotic expression systems. In contrast, although its contribution has been underestimated because of technical issues, Escherichia coli is by far the best-adapted host for such labeling. As it is now tightly controlled, we show in this review that bacterial expression can provide an NMR spectral resolution never achieved in the GPCR field.

Published
2018

5. NMR Spectroscopy for the Characterization of GPCR Energy Landscapes

Author

Jean-Louis Banères, Marina Casiraghi, and Laurent Catoire

Subjects
Ligand efficiency, Chemistry, Allosteric regulation, Biophysics, Energy landscape, Context (language use), Nuclear magnetic resonance spectroscopy, Signal transduction, Conformational ensembles, G protein-coupled receptor
Abstract

G protein-coupled receptor (GPCR)-mediated signal transduction has a central role in human physiology and implication in many diseases. Despite the tremendous number of X-ray crystallography structures published in the past decade, the molecular mechanisms of ligand-dependent signaling remain to be completed. In particular, very little information is available concerning the implication of receptor dynamics and conformational changes on GPCR ligand efficiency and coupling. In this context, mapping the conformational landscape of GPCRs, and how it is modulated by the membrane environment and allosteric and signaling partners, is fundamental in order to gain a clear picture of how the signaling mechanism proceeds. Solution-state nuclear magnetic resonance (NMR) is a powerful technique to study GPCR energy landscapes, i.e., conformational ensembles along activation and inactivation pathway, and associated kinetic barriers.

Published
2017

6. Functional Modulation of a G Protein-Coupled Receptor Conformational Landscape in a Lipid Bilayer

Author

Elodie Point, Karine Moncoq, Marina Casiraghi, Ewen Lescop, Jean-Louis Banères, Marjorie Damian, Daniel Lévy, Eric Guittet, Nelly Morellet, Laurent Catoire, Jacky Marie, Physico-chimie moléculaire des membranes biologiques (PCMMB), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire de biologie physico-chimique des protéines membranaires (LBPC-PM (UMR_7099)), Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), BioImaging Cell and Tissue Core Facility (PICT-IBiSA), Institut Curie [Paris], Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut de biologie physico-chimique (IBPC), and Institut Curie

Subjects
0301 basic medicine, Agonist, Models, Molecular, medicine.drug_class, G protein, Stereochemistry, Protein Conformation, [SDV]Life Sciences [q-bio], Lipid Bilayers, Receptors, Leukotriene B4, 010402 general chemistry, Ligands, 01 natural sciences, Biochemistry, Catalysis, 03 medical and health sciences, Colloid and Surface Chemistry, Allosteric Regulation, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Receptor, Lipid bilayer, G protein-coupled receptor, Chemistry, Leukotriene B4 receptor, General Chemistry, 0104 chemical sciences, Coupling (electronics), 030104 developmental biology, Membrane, Biophysics, Signal Transduction
Abstract

International audience; Mapping the conformational landscape of G protein-coupled receptors (GPCRs), and in particular how this landscape is modulated by the membrane environment, is required to gain a clear picture of how signaling proceeds. To this end, we have developed an original strategy based on solution-state nuclear magnetic resonance combined with an efficient isotope labeling scheme. This strategy was applied to a typical GPCR, the leukotriene B4 receptor BLT2, reconstituted in a lipid bilayer. Because of this, we are able to provide direct evidence that BLT2 explores a complex landscape that includes four different conformational states for the unliganded receptor. The relative distribution of the different states is modulated by ligands and the sterol content of the membrane, in parallel with the changes in the ability of the receptor to activate its cognate G protein. This demonstrates a conformational coupling between the agonist and the membrane environment that is likely to be fundamental for GPCR signaling.

Published
2016

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