View source for 9jfk


==Cryo-EM structure of [Pen5]-urotensin (4-11)-bounded human Urotensin receptor (UTS2R)-Gq complex==
<StructureSection load='9jfk' size='340' side='right'caption='[[9jfk]], [[Resolution|resolution]] 3.23&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9jfk]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Lama_glama Lama glama] 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=9JFK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9JFK 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]] 3.23&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHO:GLYCOCHENODEOXYCHOLIC+ACID'>CHO</scene>, <scene name='pdbligand=LE1:3-SULFANYL-L-VALINE'>LE1</scene></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=9jfk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9jfk OCA], [https://pdbe.org/9jfk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9jfk RCSB], [https://www.ebi.ac.uk/pdbsum/9jfk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9jfk 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> 
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== Publication Abstract from PubMed ==
Urotensin-II (U-II) is a potent vasoconstrictor peptide that interacts with the human urotensin-II receptor (UTR), a class A G protein-coupled receptor (GPCR) that primarily couples with G(q) proteins. In this study, we present the cryo-electron microscopy structure of the miniG(q)-coupled UTR bound to the potent UTR agonist P5U, providing insights into unique ligand recognition and activation mechanisms. Unlike typical linear peptides, the cyclic structure of P5U engages the receptor's transmembrane domains through key side chain interactions involving residues F6, W7, K8, and Y9, which are crucial for receptor activation. Comparative analysis with somatostatin receptors (SSTRs) reveals distinct ligand specificity, driven by variations in side chain composition. Notably, we identify F274(6.51) as the toggle switch residue in UTR, in contrast to the classical W(6.48) seen in other GPCRs. Our findings elucidate the structural basis for UTR's G(q) coupling specificity, highlighting unique Galpha(q) interactions. This study advances the understanding of U-II signaling and offers a foundation for developing selective UTR modulators, with potential therapeutic implications for cardiovascular diseases linked to dysregulated U-II activity.

Structural insights into hormone recognition and G-protein coupling of the urotensin-II receptor.,Gao T, You C, Cao Y, Xu X, Yuan Q, Shen S, Xu HE, Duan J J Biol Chem. 2025 Nov;301(11):110794. doi: 10.1016/j.jbc.2025.110794. Epub 2025 , Oct 6. PMID:41062066<ref>PMID:41062066</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9jfk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Duan J]]
[[Category: Gao T]]
[[Category: Xu HE]]
[[Category: You C]]