Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

6B3J

3.3 angstrom phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex

Summary for 6B3J
Entry DOI10.2210/pdb6b3j/pdb
EMDB information7039
DescriptorGlucagon-like peptide 1 receptor, Exendin-P5, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (6 entities in total)
Functional Keywordsclass b g protein-coupled receptor, agonist-receptor-g protein ternary complex, glucagon-like peptide 1 receptor, active-state g protein-coupled receptor, signaling protein, phase plate, phase contrast, single particle cryo-em
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains6
Total formula weight168196.47
Authors
Primary citationLiang, Y.L.,Khoshouei, M.,Glukhova, A.,Furness, S.G.B.,Zhao, P.,Clydesdale, L.,Koole, C.,Truong, T.T.,Thal, D.M.,Lei, S.,Radjainia, M.,Danev, R.,Baumeister, W.,Wang, M.W.,Miller, L.J.,Christopoulos, A.,Sexton, P.M.,Wootten, D.
Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex.
Nature, 555:121-125, 2018
Cited by
PubMed Abstract: The class B glucagon-like peptide-1 (GLP-1) G protein-coupled receptor is a major target for the treatment of type 2 diabetes and obesity. Endogenous and mimetic GLP-1 peptides exhibit biased agonism-a difference in functional selectivity-that may provide improved therapeutic outcomes. Here we describe the structure of the human GLP-1 receptor in complex with the G protein-biased peptide exendin-P5 and a Gα heterotrimer, determined at a global resolution of 3.3 Å. At the extracellular surface, the organization of extracellular loop 3 and proximal transmembrane segments differs between our exendin-P5-bound structure and previous GLP-1-bound GLP-1 receptor structure. At the intracellular face, there was a six-degree difference in the angle of the Gαs-α5 helix engagement between structures, which was propagated across the G protein heterotrimer. In addition, the structures differed in the rate and extent of conformational reorganization of the Gα protein. Our structure provides insights into the molecular basis of biased agonism.
PubMed: 29466332
DOI: 10.1038/nature25773
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.3 Å)
Structure validation

239492

数据于2025-07-30公开中

PDB statisticsPDBj update infoContact PDBjnumon