Agonist efficacy at the β₂AR is driven by the faster association rate of the G_s protein.

ABSTRACT:

Introduction

The β₂-adrenoceptor (β₂AR) is a class A G protein-coupled receptor (GPCR). It is therapeutically relevant in asthma and chronic obstructive pulmonary disease (COPD), where β₂AR agonists relieve bronchoconstriction. The β₂AR is a prototypical GPCR for structural and biophysical studies. However, the molecular basis of agonist efficacy at the β₂AR is not understood. We hypothesised that the kinetics of GPCR-G protein interactions could play a role in determining ligand efficacy. By studying a range of agonists with varying efficacy, we examined the relationship between ligand-induced mini-G_s binding to the β₂AR and ligand efficacy, along with the ability of individual ligands to activate the G p

SUBMITTER: Harwood CR 

PROVIDER: S-EPMC11983327 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature