8ZFE

Cryo-EM structure of the mmGPR4-Gs receptor in pH7.2

8ZFE の概要

• エントリーDOI: 10.2210/pdb8zfe/pdb
• EMDBエントリー: 60053 60058
• 分子名称: G-protein coupled receptor 4 (1 entity in total)
• 機能のキーワード: ph7.2, mmgpr4, receptor, membrane protein/immune system, membrane protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41149.79

構造登録者

Wen, X.,Rong, N.K.,Yang, F.,Sun, J.P. (登録日: 2024-05-07, 公開日: 2025-02-26, 最終更新日: 2025-07-16)

主引用文献

Wen, X.,Shang, P.,Chen, H.,Guo, L.,Rong, N.,Jiang, X.,Li, X.,Liu, J.,Yang, G.,Zhang, J.,Zhu, K.,Meng, Q.,He, X.,Wang, Z.,Liu, Z.,Cheng, H.,Zheng, Y.,Zhang, B.,Pang, J.,Liu, Z.,Xiao, P.,Chen, Y.,Liu, L.,Luo, F.,Yu, X.,Yi, F.,Zhang, P.,Yang, F.,Deng, C.,Sun, J.P.
Evolutionary study and structural basis of proton sensing by Mus GPR4 and Xenopus GPR4.
Cell, 188:653-670.e24, 2025

PubMed Abstract: Animals have evolved pH-sensing membrane receptors, such as G-protein-coupled receptor 4 (GPR4), to monitor pH changes related to their physiology and generate adaptive reactions. However, the evolutionary trajectory and structural mechanism of proton sensing by GPR4 remain unresolved. Here, we observed a positive correlation between the optimal pH of GPR4 activity and the blood pH range across different species. By solving 7-cryoelectron microscopy (cryo-EM) structures of Xenopus tropicalis GPR4 (xtGPR4) and Mus musculus GPR4 (mmGPR4) under varying pH conditions, we identified that protonation of H and H enabled polar network establishment and tighter association between the extracellular loop 2 (ECL2) and 7 transmembrane (7TM) domain, as well as a conserved propagating path, which are common mechanisms underlying protonation-induced GPR4 activation across different species. Moreover, protonation of distinct extracellular H contributed to the more acidic optimal pH range of xtGPR4. Overall, our study revealed common and distinct mechanisms of proton sensing by GPR4, from a structural, functional, and evolutionary perspective.

PubMed: 39753131
DOI: 10.1016/j.cell.2024.12.001

実験手法

ELECTRON MICROSCOPY (2.56 Å)