Time-resolved cryo-EM of G-protein activation by a GPCR.

ABSTRACT: G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by stimulating guanine nucleotide exchange in the Gα subunit¹. To visualize this mechanism, we developed a time-resolved cryo-EM approach that examines the progression of ensembles of pre-steady-state intermediates of a GPCR-G-protein complex. By monitoring the transitions of the stimulatory G_s protein in complex with the β₂-adrenergic receptor at short sequential time points after GTP addition, we identified the conformational trajectory underlying G-protein activation and functional dissociation from the receptor. Twenty structures generated from sequential overlapping particle subsets along this trajectory, compared to control structures, provide a high-resolution description of the o

SUBMITTER: Papasergi-Scott MM 

PROVIDER: S-EPMC11734571 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature