7F9Z

GHRP-6-bound ghrelin receptor in complex with Gq

7F9Z の概要

• エントリーDOI: 10.2210/pdb7f9z/pdb
• EMDBエントリー: 31501
• 分子名称: Engineered G-alpha-q, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, 3-PYRIDIN-4-YL-2,4-DIHYDRO-INDENO[1,2-.C.]PYRAZOLE, ... (7 entities in total)
• 機能のキーワード: ghrelin, gpcr, gq, membrane protein, ghrp-6
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 213178.88

構造登録者

Wang, Y.,Zhuang, Y.,Xu, P.,Xu, H.E.,Jiang, Y. (登録日: 2021-07-05, 公開日: 2021-08-18, 最終更新日: 2025-07-02)

主引用文献

Wang, Y.,Guo, S.,Zhuang, Y.,Yun, Y.,Xu, P.,He, X.,Guo, J.,Yin, W.,Xu, H.E.,Xie, X.,Jiang, Y.
Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor.
Nat Commun, 12:5064-5064, 2021

PubMed Abstract: Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of G-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor.

PubMed: 34417468
DOI: 10.1038/s41467-021-25364-2

実験手法

ELECTRON MICROSCOPY (3.2 Å)