Domain coupling in GPCRs: the engine for induced conformational changes.

ABSTRACT: Recent solved structures of G protein-coupled receptors (GPCRs) provide insights into variation of the structure and molecular mechanisms of GPCR activation. In this review, we provide evidence for the emerging paradigm of domain coupling facilitated by intrinsic disorder of the ligand-free state in GPCRs. The structure-function and dynamic studies suggest that ligand-bound GPCRs exhibit multiple active conformations in initiating cellular signals. Long-range intramolecular and intermolecular interactions at distant sites on the same receptor are crucial factors that modulate signaling function of GPCRs. Positive or negative coupling between the extracellular, the transmembrane and the intracellular domains facilitates cooperativity of activating 'switches' as requirements for the function

SUBMITTER: Unal H 

PROVIDER: S-EPMC3273637 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature