Efficacy of the β₂-adrenergic receptor is determined by conformational equilibrium in the transmembrane region.

ABSTRACT: Many drugs that target G-protein-coupled receptors (GPCRs) induce or inhibit their signal transduction with different strengths, which affect their therapeutic properties. However, the mechanism underlying the differences in the signalling levels is still not clear, although several structures of GPCRs complexed with ligands determined by X-ray crystallography are available. Here we utilized NMR to monitor the signals from the methionine residue at position 82 in neutral antagonist- and partial agonist-bound states of β(2)-adrenergic receptor (β(2)AR), which are correlated with the conformational changes of the transmembrane regions upon activation. We show that this residue exists in a conformational equilibrium between the inverse agonist-bound states and the full agonist-bound state, an

SUBMITTER: Kofuku Y 

PROVIDER: S-EPMC3658005 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature