Functional Modulation of a G Protein-Coupled Receptor Conformational Landscape in a Lipid Bilayer
| Autor: | Elodie Point, Karine Moncoq, Marina Casiraghi, Ewen Lescop, Jean-Louis Banères, Marjorie Damian, Daniel Lévy, Eric Guittet, Nelly Morellet, Laurent Catoire, Jacky Marie |
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| Přispěvatelé: | 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), Institut Curie |
| Rok vydání: | 2016 |
| Předmět: |
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 |
| Zdroj: | Journal of the American Chemical Society Journal of the American Chemical Society, American Chemical Society, 2016, 138 (35), pp.11170-11175. ⟨10.1021/jacs.6b04432⟩ |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.6b04432⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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