EMD-32246

Single-particle
3.78 Å
EMD-32246 Deposition: 18/11/2021
Map released: 27/07/2022
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-32246

Cryo-EM structure of a monomeric GPCR-Gi complex with peptide

EMD-32246

Single-particle
3.78 Å
EMD-32246 Deposition: 18/11/2021
Map released: 27/07/2022
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: GPCR-Gi Complex
Fitted models: 7w0o (Avg. Q-score: 0.285)

Deposition Authors: Xu F , Yue Y
Structural insight into apelin receptor-G protein stoichiometry.
Yue Y, Liu L, Wu LJ , Wu Y , Wang L, Li F, Liu J, Han GW, Chen B, Lin X , Brouillette RL , Breault E , Longpre JM , Shi S, Lei H, Sarret P , Stevens RC, Hanson MA , Xu F
(2022) Nat Struct Mol Biol , 29 , 688 - 697
PUBMED: 35817871
DOI: doi:10.1038/s41594-022-00797-5
ISSN: 1545-9985
Abstract:
The technique of cryogenic-electron microscopy (cryo-EM) has revolutionized the field of membrane protein structure and function with a focus on the dominantly observed molecular species. This report describes the structural characterization of a fully active human apelin receptor (APJR) complexed with heterotrimeric G protein observed in both 2:1 and 1:1 stoichiometric ratios. We use cryo-EM single-particle analysis to determine the structural details of both species from the same sample preparation. Protein preparations, in the presence of the endogenous peptide ligand ELA or a synthetic small molecule, both demonstrate these mixed stoichiometric states. Structural differences in G protein engagement between dimeric and monomeric APJR suggest a role for the stoichiometry of G protein-coupled receptor- (GPCR-)G protein coupling on downstream signaling and receptor pharmacology. Furthermore, a small, hydrophobic dimer interface provides a starting framework for additional class A GPCR dimerization studies. Together, these findings uncover a mechanism of versatile regulation through oligomerization by which GPCRs can modulate their signaling.