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

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...

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Autores principales: Louet, Maxime, Casiraghi, Marina, Damian, Marjorie, Costa, Mauricio GS, Renault, Pedro, Gomes, Antoniel AS, Batista, Paulo R, M'Kadmi, Céline, Mary, Sophie, Cantel, Sonia, Denoyelle, Severine, Ben Haj Salah, Khoubaib, Perahia, David, Bisch, Paulo M, Fehrentz, Jean-Alain, Catoire, Laurent J, Floquet, Nicolas, Banères, Jean-Louis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416020/
https://www.ncbi.nlm.nih.gov/pubmed/34477105
http://dx.doi.org/10.7554/eLife.63201
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author Louet, Maxime
Casiraghi, Marina
Damian, Marjorie
Costa, Mauricio GS
Renault, Pedro
Gomes, Antoniel AS
Batista, Paulo R
M'Kadmi, Céline
Mary, Sophie
Cantel, Sonia
Denoyelle, Severine
Ben Haj Salah, Khoubaib
Perahia, David
Bisch, Paulo M
Fehrentz, Jean-Alain
Catoire, Laurent J
Floquet, Nicolas
Banères, Jean-Louis
author_facet Louet, Maxime
Casiraghi, Marina
Damian, Marjorie
Costa, Mauricio GS
Renault, Pedro
Gomes, Antoniel AS
Batista, Paulo R
M'Kadmi, Céline
Mary, Sophie
Cantel, Sonia
Denoyelle, Severine
Ben Haj Salah, Khoubaib
Perahia, David
Bisch, Paulo M
Fehrentz, Jean-Alain
Catoire, Laurent J
Floquet, Nicolas
Banères, Jean-Louis
author_sort Louet, Maxime
collection PubMed
description 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.
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spelling pubmed-84160202021-09-09 Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor Louet, Maxime Casiraghi, Marina Damian, Marjorie Costa, Mauricio GS Renault, Pedro Gomes, Antoniel AS Batista, Paulo R M'Kadmi, Céline Mary, Sophie Cantel, Sonia Denoyelle, Severine Ben Haj Salah, Khoubaib Perahia, David Bisch, Paulo M Fehrentz, Jean-Alain Catoire, Laurent J Floquet, Nicolas Banères, Jean-Louis eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2021-09-03 /pmc/articles/PMC8416020/ /pubmed/34477105 http://dx.doi.org/10.7554/eLife.63201 Text en © 2021, Louet et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Louet, Maxime
Casiraghi, Marina
Damian, Marjorie
Costa, Mauricio GS
Renault, Pedro
Gomes, Antoniel AS
Batista, Paulo R
M'Kadmi, Céline
Mary, Sophie
Cantel, Sonia
Denoyelle, Severine
Ben Haj Salah, Khoubaib
Perahia, David
Bisch, Paulo M
Fehrentz, Jean-Alain
Catoire, Laurent J
Floquet, Nicolas
Banères, Jean-Louis
Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor
title Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor
title_full Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor
title_fullStr Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor
title_full_unstemmed Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor
title_short Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor
title_sort concerted conformational dynamics and water movements in the ghrelin g protein-coupled receptor
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416020/
https://www.ncbi.nlm.nih.gov/pubmed/34477105
http://dx.doi.org/10.7554/eLife.63201
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