Gαs slow conformational transition upon GTP binding and a novel Gαs regulator.

ABSTRACT: G proteins are major signaling partners for G protein-coupled receptors (GPCRs). Although stepwise structural changes during GPCR-G protein complex formation and guanosine diphosphate (GDP) release have been reported, no information is available with regard to guanosine triphosphate (GTP) binding. Here, we used a novel Bayesian integrative modeling framework that combines data from hydrogen-deuterium exchange mass spectrometry, tryptophan-induced fluorescence quenching, and metadynamics simulations to derive a kinetic model and atomic-level characterization of stepwise conformational changes incurred by the β₂-adrenergic receptor (β₂AR)-Gs complex after GDP release and GTP binding. Our data suggest rapid GTP binding and GTP-induced dissociation of Gαs from β₂

SUBMITTER: Ahn D 

PROVIDER: S-EPMC10148139 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature