View source for 8zfz


==cryo-EM structure of Gs-coupled zebrafish GPR4 at pH 6.5==
<StructureSection load='8zfz' size='340' side='right'caption='[[8zfz]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8zfz]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio], [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [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=8ZFZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZFZ 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]] 3.3&#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=8zfz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zfz OCA], [https://pdbe.org/8zfz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zfz RCSB], [https://www.ebi.ac.uk/pdbsum/8zfz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zfz 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 ==
G protein-coupled receptor 4 (GPR4) belongs to the subfamily of proton-sensing GPCRs (psGPCRs), which detect pH changes in extracellular environment and regulate diverse physiological responses. GPR4 was found to be overactivated in acidic tumor microenvironment as well as inflammation sites, with a triad of acidic residues within the transmembrane domain identified as crucial for proton sensing. However, the 3D structure remains unknown, and the roles of other conserved residues within psGPCRs are not well understood. Here we report cryo-electron microscopy (cryo-EM) structures of active zebrafish GPR4 at both pH 6.5 and 8.5, each highlighting a distribution of histidine and acidic residues at the extracellular region. Cell-based assays show that these ionizable residues moderately influence the proton-sensing capacity of zebrafish GPR4, compared to the more significant effects of the triad residues. Furthermore, we reveal a cluster of aromatic residues within the orthosteric pocket that may propagate the signaling to the intercellular region via repacking the aromatic patch at the central region. This study provides a framework for future signaling and functional investigation of psGPCRs.

Cryo-EM structure of an activated GPR4-Gs signaling complex.,Ma Y, Wang Y, Tang M, Weng Y, Chen Y, Xu Y, An S, Wu Y, Zhao S, Xu H, Li D, Liu M, Lu W, Ru H, Song G Nat Commun. 2025 Jan 11;16(1):605. doi: 10.1038/s41467-025-55901-2. PMID:39799123<ref>PMID:39799123</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8zfz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Danio rerio]]
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Synthetic construct]]
[[Category: Ma Y]]
[[Category: Ru H]]
[[Category: Song G]]
[[Category: Tang M]]