Minute-scale persistence of a GPCR conformation state triggered by non-cognate G protein interactions primes signaling.

ABSTRACT: Despite the crowded nature of the cellular milieu, ligand-GPCR-G protein interactions are traditionally viewed as spatially and temporally isolated events. In contrast, recent reports suggest the spatial and temporal coupling of receptor-effector interactions, with the potential to diversify downstream responses. In this study, we combine protein engineering of GPCR-G protein interactions with affinity sequestration and photo-manipulation of the crucial Gα C terminus, to demonstrate the temporal coupling of cognate and non-cognate G protein interactions through priming of the GPCR conformation. We find that interactions of the Gαs and Gαq C termini with the β₂-adrenergic receptor (β₂-AR), targeted at the G-protein-binding site, enhance Gs activation and cyclic AMP lev

SUBMITTER: Gupte TM 

PROVIDER: S-EPMC6811539 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature