Molecular Dynamics Simulations of the Allosteric Modulation of the Adenosine A2a Receptor by a Mini-G Protein - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2019

Molecular Dynamics Simulations of the Allosteric Modulation of the Adenosine A2a Receptor by a Mini-G Protein

Résumé

Through their coupling to G proteins, G Protein-Coupled Receptors (GPCRs) trigger cellular responses to various signals. Some recent experiments have interestingly demonstrated that the G protein can also act on the receptor by favoring a closed conformation of its orthosteric site, even in the absence of a bound agonist. In this work, we explored such an allosteric modulation by performing extensive molecular dynamics simulations on the adenosine A2 receptor (A2AR) coupled to the Mini-Gs protein. In the presence of the Mini-Gs, we confirmed a restriction of the receptor’s agonist binding site that can be explained by a modulation of the intrinsic network of contacts of the receptor. Of interest, we observed similar effects with the C-terminal helix of the Mini-Gs, showing that the observed effect on the binding pocket results from direct local contacts with the bound protein partner that cause a rewiring of the whole receptor’s interaction network.
Fichier principal
Vignette du fichier
s41598-019-41980-x.pdf (2.18 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-02322127 , version 1 (02-03-2021)

Licence

Identifiants

Citer

Pedro Renault, Maxime Louet, Jacky Marie, Gilles Labesse, Nicolas Floquet. Molecular Dynamics Simulations of the Allosteric Modulation of the Adenosine A2a Receptor by a Mini-G Protein. Scientific Reports, 2019, 9 (1), ⟨10.1038/s41598-019-41980-x⟩. ⟨hal-02322127⟩
64 Consultations
36 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More