Ligands and signaling proteins govern the conformational landscape explored by a G protein-coupled receptor.

ABSTRACT: The dynamic character of G protein-coupled receptors is essential to their function. However, the details of how ligands stabilize a particular conformation to selectively activate a signaling pathway and how signaling proteins affect this conformational repertoire remain unclear. Using a prototypical peptide-activated class A G protein-coupled receptor (GPCR), the ghrelin receptor, reconstituted as a monomer into lipid discs and labeled with a fluorescent conformational reporter, we demonstrate that ligand efficacy and functional selectivity are directly related to different receptor conformations. Of importance, our data bring direct evidence that distinct effector proteins affect the conformational landscape of the ghrelin receptor in different ways. Whereas G proteins affect the balanc

SUBMITTER: Mary S 

PROVIDER: S-EPMC3361445 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature