Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound β₁-Adrenergic Receptor.

ABSTRACT: Cardiac disease remains the leading cause of morbidity and mortality worldwide. The β₁-adrenergic receptor (β₁-AR) is a major regulator of cardiac functions and is downregulated in the majority of heart failure cases. A key physiological process is the activation of heterotrimeric G-protein Gs by β₁-ARs, leading to increased heart rate and contractility. Here, we use cryo-electron microscopy and functional studies to investigate the molecular mechanism by which β₁-AR activates Gs. We find that the tilting of α5-helix breaks a hydrogen bond between the sidechain of His373 in the C-terminal α5-helix and the backbone carbonyl of Arg38 in the N-terminal αN-helix of Gα_s. Together with the disruption of another interacting network involving

SUBMITTER: Su M 

PROVIDER: S-EPMC7541785 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature