View source for 8zf9


==Cryo-EM structure of the mmGPR4-Gs complex in pH7.2==
<StructureSection load='8zf9' size='340' side='right'caption='[[8zf9]], [[Resolution|resolution]] 2.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8zf9]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ZF9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZF9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.56&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8zf9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zf9 OCA], [https://pdbe.org/8zf9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zf9 RCSB], [https://www.ebi.ac.uk/pdbsum/8zf9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zf9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:39753131</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8zf9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Synthetic construct]]
[[Category: Rong NK]]
[[Category: Sun JP]]
[[Category: Wen X]]
[[Category: Yang F]]