5VAI

Cryo-EM structure of the activated Glucagon-like peptide-1 receptor in complex with G protein

Summary for 5VAI

• Entry DOI: 10.2210/pdb5vai/pdb
• EMDB information: 8653
• Descriptor: Uncharacterized protein, Glucagon-like peptide 1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (6 entities in total)
• Functional Keywords: class b gpcr, glp-1, glp-1r, complex, signaling protein-hormone complex, signaling protein/hormone
• Biological source: Oryctolagus cuniculus (Rabbit); More
• Total number of polymer chains: 6
• Total formula weight: 161760.52

Authors

Zhang, Y.,Sun, B.,Feng, D.,Hu, H.,Chu, M.,Qu, Q.,Tarrasch, J.T.,Li, S.,Kobilka, T.S.,Kobilka, B.K.,Skiniotis, G. (deposition date: 2017-03-27, release date: 2017-05-24, Last modification date: 2025-05-14)

Primary citation

Zhang, Y.,Sun, B.,Feng, D.,Hu, H.,Chu, M.,Qu, Q.,Tarrasch, J.T.,Li, S.,Sun Kobilka, T.,Kobilka, B.K.,Skiniotis, G.
Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.
Nature, 546:248-253, 2017

PubMed 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. 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 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. Conformational changes in the transmembrane domain result in a sharp kink in the middle of transmembrane helix 6, which pivots its intracellular half outward to accommodate the α5-helix of the Ras-like domain of G. These results provide a structural framework for understanding class B GPCR activation through hormone binding.

PubMed: 28538729
DOI: 10.1038/nature22394

Experimental method

ELECTRON MICROSCOPY (4.1 Å)