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

eLife

Pedro Renault¹  Jean-Louis Banères¹  Marjorie Damian¹  Severine Denoyelle¹  Maxime Louet¹  Sophie Mary¹  Céline M'Kadmi¹  Khoubaib Ben Haj Salah¹  Jean-Alain Fehrentz¹  Nicolas Floquet¹  Sonia Cantel¹  Antoniel AS Gomes²  Marina Casiraghi³  Laurent J Catoire³  David Perahia⁴  Mauricio GS Costa⁵  Paulo M Bisch⁶  Paulo R Batista⁷ 

[1] IBMM, Univ Montpellier, CNRS, ENSCM, Montpellier, France;IBMM, Univ Montpellier, CNRS, ENSCM, Montpellier, France;Laboratório de Física Biológica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS, Université de Paris, Institut de Biologie Physico-Chimique (FRC 550), Paris, France;Laboratoire de Biologie et Pharmacologie Appliquées, UMR 8113 CNRS, Ecole Normale Supérieure Paris-Saclay, Gif-sur-Yvette, France;Laboratoire de Biologie et Pharmacologie Appliquées, UMR 8113 CNRS, Ecole Normale Supérieure Paris-Saclay, Gif-sur-Yvette, France;Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;Laboratório de Física Biológica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;

关键词: GPCR;    hydration;    signaling;    E. coli;    Human;   

DOI  :  10.7554/eLife.63201

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY