Binding kinetics drive G protein subtype selectivity at the β₁-adrenergic receptor.

ABSTRACT: G protein-coupled receptors (GPCRs) bind to different G protein α-subtypes with varying degrees of selectivity. The mechanism by which GPCRs achieve this selectivity is still unclear. Using ¹³C methyl methionine and ¹⁹F NMR, we investigate the agonist-bound active state of β₁AR and its ternary complexes with different G proteins in solution. We find the receptor in the ternary complexes adopts very similar conformations. In contrast, the full agonist-bound receptor active state assumes a conformation differing from previously characterised activation intermediates or from β₁AR in ternary complexes. Assessing the kinetics of binding for the agonist-bound receptor with different G proteins, we find the increased affinity of β₁AR for G

SUBMITTER: Jones AJY 

PROVIDER: S-EPMC10864275 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature