eLife (Sep 2021)

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

  • Maxime Louet,
  • Marina Casiraghi,
  • Marjorie Damian,
  • Mauricio GS Costa,
  • Pedro Renault,
  • Antoniel AS Gomes,
  • Paulo R Batista,
  • Céline M'Kadmi,
  • Sophie Mary,
  • Sonia Cantel,
  • Severine Denoyelle,
  • Khoubaib Ben Haj Salah,
  • David Perahia,
  • Paulo M Bisch,
  • Jean-Alain Fehrentz,
  • Laurent J Catoire,
  • Nicolas Floquet,
  • Jean-Louis Banères

DOI
https://doi.org/10.7554/eLife.63201
Journal volume & issue
Vol. 10

Abstract

Read online

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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