Polar transmembrane interactions drive formation of ligand-specific and signal pathway-biased family B G protein-coupled receptor conformations.

ABSTRACT: Recently, the concept of ligand-directed signaling--the ability of different ligands of an individual receptor to promote distinct patterns of cellular response--has gained much traction in the field of drug discovery, with the potential to sculpt biological response to favor therapeutically beneficial signaling pathways over those leading to harmful effects. However, there is limited understanding of the mechanistic basis underlying biased signaling. The glucagon-like peptide-1 receptor is a major target for treatment of type-2 diabetes and is subject to ligand-directed signaling. Here, we demonstrate the importance of polar transmembrane residues conserved within family B G protein-coupled receptors, not only for protein folding and expression, but also in controlling activation transiti

SUBMITTER: Wootten D 

PROVIDER: S-EPMC3612682 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature