7W0P

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

7W0P の概要

• エントリーDOI: 10.2210/pdb7w0p/pdb
• EMDBエントリー: 32247
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• 機能のキーワード: complex, gpcr, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 175925.21

構造登録者

Xu, F.,Yue, Y.,Liu, L.E.,Wu, L.J.,Hanson, M. (登録日: 2021-11-18, 公開日: 2022-07-27)

主引用文献

Yue, Y.,Liu, L.,Wu, L.J.,Wu, Y.,Wang, L.,Li, F.,Liu, J.,Han, G.W.,Chen, B.,Lin, X.,Brouillette, R.L.,Breault, E.,Longpre, J.M.,Shi, S.,Lei, H.,Sarret, P.,Stevens, R.C.,Hanson, M.A.,Xu, F.
Structural insight into apelin receptor-G protein stoichiometry.
Nat.Struct.Mol.Biol., 29:688-697, 2022

PubMed 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.

PubMed: 35817871
DOI: 10.1038/s41594-022-00797-5

実験手法

ELECTRON MICROSCOPY (3.16 Å)