Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor:Gq complex

Marjorie Damian; Sophie Mary; Mathieu Maingot; Céline M'Kadmi; Didier Gagne; Jean-Philippe Leyris; Séverine Denoyelle; Gérald Gaibelet; Laurent Gavara; Mauricio Garcia de Souza Costa; David Perahia; Eric Trinquet; Bernard Mouillac; Ségolène Galandrin; Céline Galès; Jean-Alain Fehrentz; Nicolas Floquet; Jean Martinez; Jacky Marie; Jean-Louis Banères

doi:10.1073/pnas.1414618112

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Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor:Gq complex

Journal article

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Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor:Gq complex

Marjorie Damian, Sophie Mary, Mathieu Maingot, Céline M'Kadmi, Didier Gagne, Jean-Philippe Leyris, Séverine Denoyelle, Gérald Gaibelet, Laurent Gavara, Mauricio Garcia de Souza Costa, …

Proceedings of the National Academy of Sciences of the United States of America, Vol.112(5), pp.1601-1606

03/02/2015

DOI: https://doi.org/10.1073/pnas.1414618112

Abstract

GPCR

G protein

preassembly

conformation dynamics

signaling

Significance G protein-coupled receptors (GPCRs), one of the largest cell surface receptor families, transmit their signals through the coupling of intracellular partners, such as the G proteins. Knowing how this coupling occurs is essential, because it governs the entire signaling process. To address this open question, we used a purified GPCR as a model to which we applied various state-of-the-art biochemical and biophysical approaches. By doing so, we provide direct experimental evidence of a signaling mechanism in which receptor conformational changes are directly linked to a rearrangement of a preassembled complex between the receptor and its cognate Gq protein. This sheds light on the way in which a GPCR interacts with G proteins to trigger signaling.

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Title: Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor:Gq complex
Creators - without role: Marjorie Damian - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Sophie Mary - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Mathieu Maingot - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Céline M'Kadmi - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Didier Gagne - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Jean-Philippe Leyris - Institut des Biomolécules Max Mousseron
Séverine Denoyelle - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Gérald Gaibelet - Institut de Génomique Fonctionnelle
Laurent Gavara - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Mauricio Garcia de Souza Costa - Laboratoire de Biologie et de Pharmacologie Appliquée
David Perahia - Laboratoire de Biologie et Pharmacologie Appliquée
Eric Trinquet - Université de Montpellier, Institut de Génomique Fonctionnelle - IGF
Bernard Mouillac - Université de Montpellier, Institut de Génomique Fonctionnelle - IGF
Ségolène Galandrin - Institut des Maladies Métaboliques et Cardiovasculaires
Céline Galès - Institut des Maladies Métaboliques et Cardiovasculaires
Jean-Alain Fehrentz - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Nicolas Floquet - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Jean Martinez - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Jacky Marie - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Jean-Louis Banères - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Publication Details: Proceedings of the National Academy of Sciences of the United States of America, Vol.112(5), pp.1601-1606
Grant note: PCV08-323163
Identifiers: 9935474709311
Academic Unit: Institut de Génomique Fonctionnelle - IGF; Institut des Biomolécules Max Mousseron - IBMM
Language: English
Resource Type: Journal article
Local Fields: hal-04687085