title: Functional Modulation of a G Protein-Coupled Receptor Conformational Landscape in a Lipid Bilayer.
abstract: 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.
authors.affiliation: Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université Paris Diderot, Sorbonne Paris Cité, Institut de Biologie Physico-Chimique (FRC 550) , 13 rue Pierre et Marie Curie, F-75005 Paris, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Casiraghi
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier-ENSCM, Faculté de Pharmacie , 15 Avenue C. Flahault, F-34093 Montpellier, France.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Damian
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud , 91198 Gif-sur-Yvette, France.
authors.forename: Ewen
authors.initials: E
authors.lastname: Lescop
authors.affiliation: Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université Paris Diderot, Sorbonne Paris Cité, Institut de Biologie Physico-Chimique (FRC 550) , 13 rue Pierre et Marie Curie, F-75005 Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Point
authors.affiliation: Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université Paris Diderot, Sorbonne Paris Cité, Institut de Biologie Physico-Chimique (FRC 550) , 13 rue Pierre et Marie Curie, F-75005 Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Moncoq
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud , 91198 Gif-sur-Yvette, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Morellet
authors.affiliation: Institut Curie , Centre de Recherche, 75231 Paris, France.|UMR 168, CNRS , 75231 Paris, France.|Université Pierre et Marie Curie , F-75248 Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier-ENSCM, Faculté de Pharmacie , 15 Avenue C. Flahault, F-34093 Montpellier, France.
authors.forename: Jacky
authors.initials: J
authors.lastname: Marie
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud , 91198 Gif-sur-Yvette, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Guittet
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier-ENSCM, Faculté de Pharmacie , 15 Avenue C. Flahault, F-34093 Montpellier, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Banères
authors.affiliation: Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université Paris Diderot, Sorbonne Paris Cité, Institut de Biologie Physico-Chimique (FRC 550) , 13 rue Pierre et Marie Curie, F-75005 Paris, France.
authors.forename: Laurent J
authors.initials: LJ
authors.lastname: Catoire
mesh_terms: D000494:Allosteric Regulation; D008024:Ligands; D008051:Lipid Bilayers / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D018102:Receptors, Leukotriene B4 / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D008051:Lipid Bilayers; D018102:Receptors, Leukotriene B4