Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.

ABSTRACT: Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR) that signals primarily through the stimulatory G protein G_s. Class B GPCRs are important therapeutic targets; however, our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors. Here we report the cryo-electron microscopy structure of the peptide-activated GLP-1R-G_s complex at near atomic resolution. The peptide is clasped between the N-terminal domain and the transmembrane core of the receptor, and further stabilized by extracellular loops.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC5587415 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature