8zf6

Cryo-EM structure of the xGPR4-Gs complex in pH6.7

spinqualitylabelsall models 8zf6, resolution 2.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8zf6 is a 5 chain structure with sequence from Homo sapiens, Xenopus tropicalis and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.98Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A6I8PUB9_XENTR Publication Abstract from PubMed 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(ECL2-45.47) and H(7.36) 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(ECL2-45.41) 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. Evolutionary study and structural basis of proton sensing by Mus GPR4 and Xenopus GPR4.,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 JP Cell. 2025 Feb 6;188(3):653-670.e24. doi: 10.1016/j.cell.2024.12.001. Epub 2025 , Jan 2. PMID:39753131 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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