7W0L

Cryo-EM structure of a dimeric GPCR-Gi complex with small molecule

Summary for 7W0L

• Entry DOI: 10.2210/pdb7w0l/pdb
• EMDB information: 32243
• Descriptor: 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)
• Functional Keywords: complex, gpcr, dimerization, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 223298.45

Authors

Yue, Y.,Liu, L.E.,Wu, L.J.,Xu, F.,Hanson, M. (deposition date: 2021-11-18, release date: 2022-07-27, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.57 Å)