8XQE

Cryo-EM structure of human dimeric APJR-Gi complex with apelin-13.

8XQE の概要

• エントリーDOI: 10.2210/pdb8xqe/pdb
• EMDBエントリー: 38574
• 分子名称: G protein subunit alpha i1, 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: gpcr, apjr, gi, apelin-13, dimeric, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 223859.20

構造登録者

Yue, Y.,Liu, L.E.,Wu, L.J.,Xu, F. (登録日: 2024-01-05, 公開日: 2025-01-22, 最終更新日: 2025-07-02)

主引用文献

Yue, Y.,Liu, L.,Wu, L.,Xu, C.,Na, M.,Liu, S.,Liu, Y.,Li, F.,Liu, J.,Shi, S.,Lei, H.,Zhao, M.,Yang, T.,Ji, W.,Wang, A.,Hanson, M.A.,Stevens, R.C.,Liu, J.,Xu, F.
Structural insights into the regulation of monomeric and dimeric apelin receptor.
Nat Commun, 16:310-310, 2025

PubMed Abstract: The apelin receptor (APJR) emerges as a promising drug target for cardiovascular health and muscle regeneration. While prior research unveiled the structural versatility of APJR in coupling to Gi proteins as a monomer or dimer, the dynamic regulation within the APJR dimer during activation remains poorly understood. In this study, we present the structures of the APJR dimer and monomer complexed with its endogenous ligand apelin-13. In the dimeric structure, apelin-13 binds exclusively to one protomer that is coupled with Gi proteins, revealing a distinct ligand-binding behavior within APJR homodimers. Furthermore, binding of an antagonistic antibody induces a more compact dimerization by engaging both protomers. Notably, structural analyses of the APJR dimer complexed with an agonistic antibody, with or without Gi proteins, suggest that G protein coupling may promote the dissociation of the APJR dimer during activation. These findings underscore the intricate interplay between ligands, dimerization, and G protein coupling in regulating APJR signaling pathways.

PubMed: 39747115
DOI: 10.1038/s41467-024-55555-6

実験手法

ELECTRON MICROSCOPY (3.48 Å)