View source for 9jft


==Cryo-EM structure of GPR65 complexed with miniGs in pH6.5==
<StructureSection load='9jft' size='340' side='right'caption='[[9jft]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9jft]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9JFT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9JFT 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]] 3.27&#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=9jft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9jft OCA], [https://pdbe.org/9jft PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9jft RCSB], [https://www.ebi.ac.uk/pdbsum/9jft PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9jft 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 ==
The regulation of pH homeostasis is crucial in many biological processes vital for survival, growth, and function of life. The pH-sensing G protein-coupled receptors (GPCRs), including GPR4, GPR65 and GPR68, play a pivotal role in detecting changes in extracellular proton concentrations, impacting both physiological and pathological states. However, comprehensive understanding of the proton sensing mechanism is still elusive. Here, we determined the cryo-electron microscopy structures of GPR4 and GPR65 in various activation states across different pH levels, coupled with G(s), G(q) or G(13) proteins, as well as a small molecule NE52-QQ57-bound inactive GPR4 structure. These structures reveal the dynamic nature of the extracellular loop 2 and its signature conformations in different receptor states, and disclose the proton sensing mechanism mediated by networks of extracellular histidine and carboxylic acid residues. Notably, we unexpectedly captured partially active intermediate states of both GPR4-G(s) and GPR4-G(q) complexes, and identified a unique allosteric binding site for NE52-QQ57 in GPR4. By integrating prior investigations with our structural analysis and mutagenesis data, we propose a detailed atomic model for stepwise proton sensation and GPCR activation. These insights may pave the way for the development of selective ligands and targeted therapeutic interventions for pH sensing-relevant diseases.

Structural basis of stepwise proton sensing-mediated GPCR activation.,Yue X, Peng L, Liu S, Zhang B, Zhang X, Chang H, Pei Y, Li X, Liu J, Shui W, Wu L, Xu H, Liu ZJ, Hua T Cell Res. 2025 Apr 11. doi: 10.1038/s41422-025-01092-w. PMID:40211064<ref>PMID:40211064</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9jft" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Hua T]]
[[Category: Liu ZJ]]
[[Category: Wu LJ]]
[[Category: Yue XL]]