8HCQ

Cryo-EM structure of endothelin1-bound ETAR-Gq complex

8HCQ の概要

• エントリーDOI: 10.2210/pdb8hcq/pdb
• EMDBエントリー: 34663
• 分子名称: Guanine nucleotide-binding protein G(q) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, scFv16, ... (6 entities in total)
• 機能のキーワード: et1, etar, gq, scfv16, membrane protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 179832.74

構造登録者

Yuan, Q.,Jiang, Y.,Xu, H.E.,Ji, Y.,Duan, J. (登録日: 2022-11-02, 公開日: 2023-03-22, 最終更新日: 2024-11-20)

主引用文献

Ji, Y.,Duan, J.,Yuan, Q.,He, X.,Yang, G.,Zhu, S.,Wu, K.,Hu, W.,Gao, T.,Cheng, X.,Jiang, H.,Eric Xu, H.,Jiang, Y.
Structural basis of peptide recognition and activation of endothelin receptors.
Nat Commun, 14:1268-1268, 2023

PubMed Abstract: Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ETR) and B (ETR). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothelial cell-derived vasoconstrictor peptides with long-lasting actions, the endothelin system has attracted extensive attention due to its critical role in vasoregulation and close relevance in cardiovascular-related diseases. Here we present three cryo-electron microscopy structures of ETR and ETR bound to ET-1 and ETR bound to the selective peptide IRL1620. These structures reveal a highly conserved recognition mode of ET-1 and characterize the ligand selectivity by ETRs. They also present several conformation features of the active ETRs, thus revealing a specific activation mechanism. Together, these findings deepen our understanding of endothelin system regulation and offer an opportunity to design selective drugs targeting specific ETR subtypes.

PubMed: 36882417
DOI: 10.1038/s41467-023-36998-9

実験手法

ELECTRON MICROSCOPY (3.01 Å)