Mechanistic insights into G-protein coupling with an agonist-bound G-protein-coupled receptor.

ABSTRACT: G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by promoting guanine nucleotide exchange. Here, we investigate the coupling of G proteins with GPCRs and describe the events that ultimately lead to the ejection of GDP from its binding pocket in the Gα subunit, the rate-limiting step during G-protein activation. Using molecular dynamics simulations, we investigate the temporal progression of structural rearrangements of GDP-bound G_s protein (G_s·GDP; hereafter G_s^GDP) upon coupling to the β₂-adrenergic receptor (β₂AR) in atomic detail. The binding of G_s^GDP to the β₂AR is followed by long-range allosteric effects that significantly reduce the energy needed for GDP release: t

SUBMITTER: Batebi H 

PROVIDER: S-EPMC12132790 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature