Ligand-dependent perturbation of the conformational ensemble for the GPCR β2 adrenergic receptor revealed by HDX.

ABSTRACT: Mechanism of G protein-coupled receptor (GPCR) activation and their modulation by functionally distinct ligands remains elusive. Using the technique of amide hydrogen/deuterium exchange coupled with mass spectrometry, we examined the ligand-induced changes in conformational states and stability within the beta-2-adrenergic receptor (β(2)AR). Differential HDX reveals ligand-specific alterations in the energy landscape of the receptor's conformational ensemble. The inverse agonists timolol and carazolol were found to be most stabilizing even compared with the antagonist alprenolol, notably in intracellular regions where G proteins are proposed to bind, while the agonist isoproterenol induced the largest degree of conformational mobility. The partial agonist clenbuterol displayed conformation

SUBMITTER: West GM 

PROVIDER: S-EPMC3196059 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature