Identification of two distinct inactive conformations of the beta2-adrenergic receptor reconciles structural and biochemical observations.

ABSTRACT: Fully understanding the mechanisms of signaling proteins such as G protein-coupled receptors (GPCRs) will require the characterization of their conformational states and the pathways connecting those states. The recent crystal structures of the beta(2)- and beta(1)-adrenergic receptors in a nominally inactive state constituted a major advance toward this goal, but also raised new questions. Although earlier biochemical observations had suggested that these receptors possessed a set of contacts between helices 3 and 6, known as the ionic lock, which was believed to form a molecular switch for receptor activation, the crystal structures lacked these contacts. The unexpectedly broken ionic lock has raised questions about the true conformation(s) of the inactive state and the role of the ionic

SUBMITTER: Dror RO 

PROVIDER: S-EPMC2650503 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature