9jvh

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Current revision (19:23, 26 February 2025) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 9jvh is ON HOLD until Paper Publication
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==Cryo-EM structure of the mmGPR4-Gs receptor in pH6.2==
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<StructureSection load='9jvh' size='340' side='right'caption='[[9jvh]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[9jvh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9JVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9JVH FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.76&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9jvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9jvh OCA], [https://pdbe.org/9jvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9jvh RCSB], [https://www.ebi.ac.uk/pdbsum/9jvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9jvh ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GPR4_MOUSE GPR4_MOUSE] Proton-sensing G-protein coupled receptor couples to multiple intracellular signaling pathways, including GNAS/cAMP, GNAQ/phospholipase C (PLC), and GNA12/GNA13/Rho pathways (PubMed:17145776). Acidosis-induced GPR4 activation increases paracellular gap formation and permeability of vascular endothelial cells through the GNA12/GNA13/Rho GTPase signaling pathway (PubMed:32058960). In the brain may mediate central respiratory sensitivity to CO(2)/H(+) (PubMed:26068853).<ref>PMID:17145776</ref> <ref>PMID:26068853</ref> <ref>PMID:32058960</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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Authors: Wen, X., Rong, N.K., Yang, F., Sun, J.P.
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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>
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Description: Cryo-EM structure of the mmGPR4-Gs receptor in pH6.2
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Yang, F]]
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<div class="pdbe-citations 9jvh" style="background-color:#fffaf0;"></div>
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[[Category: Wen, X]]
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== References ==
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[[Category: Sun, J.P]]
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<references/>
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[[Category: Rong, N.K]]
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Mus musculus]]
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[[Category: Rong NK]]
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[[Category: Sun JP]]
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[[Category: Wen X]]
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[[Category: Yang F]]

Current revision

Cryo-EM structure of the mmGPR4-Gs receptor in pH6.2

PDB ID 9jvh

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