Structures of β₁-adrenergic receptor in complex with Gs and ligands of different efficacies.

ABSTRACT: G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies, and transduce to heterotrimeric G-proteins to generate different degrees of physiological responses. Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. We report the cryo-EM structures of β₁-adrenergic receptor (β₁-AR) in complex with Gs (Gα_sGβ₁Gγ₂) and a partial agonist or a very weak partial agonist, and compare them to the β₁-AR-Gs structure in complex with a full agonist. Analyses reveal similar overall complex architecture, with local conformational differences. Cellular functional studies with mutatio

SUBMITTER: Su M 

PROVIDER: S-EPMC9283524 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature