View source for 9wey


==Structure of HCMV UL33 in complex with human Gs protein==
<StructureSection load='9wey' size='340' side='right'caption='[[9wey]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9wey]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Human_betaherpesvirus_5 Human betaherpesvirus 5] 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=9WEY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WEY 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=9wey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wey OCA], [https://pdbe.org/9wey PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wey RCSB], [https://www.ebi.ac.uk/pdbsum/9wey PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wey ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBG2_HUMAN GBG2_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 (By similarity).
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== Publication Abstract from PubMed ==
Human cytomegalovirus (HCMV) encodes the orphan G protein-coupled receptor (GPCR) UL33, which exhibits constitutive activity that disrupts host G protein signalling, facilitating efficient viral replication and pathogenesis. The cryo-electron microscopy (cryo-EM) structure of UL33 bound to the G(s) subtype of G protein reveals the N-terminal peptide as a tethered ligand reminiscent of the protease-activated receptors and adhesion GPCRs. This self-agonism induces a non-canonical active state that facilitates promiscuous G protein coupling, a plausible viral strategy for fine-tuning host signalling. Structure-guided mutagenesis disrupting key interactions between the N-terminus and its binding pocket abolishes G protein-mediated signalling, confirming the role of the N-terminus as a self-agonist. Our findings elucidate the structural basis for this activation mechanism and highlight the strategies employed by HCMV to hijack host G protein signalling.

Activation of cytomegalovirus-encoded G protein-coupled receptor UL33 by an innate N-terminal peptide.,Drzazga AK, Suzuki S, Wouters C, Faas F, Nishikawa K, Kamegawa A, Fujiyoshi Y, Rosenkilde MM, Tsutsumi N Commun Biol. 2026 Feb 12. doi: 10.1038/s42003-026-09660-5. PMID:41680497<ref>PMID:41680497</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 9wey" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human betaherpesvirus 5]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Fujiyoshi Y]]
[[Category: Nishikawa K]]
[[Category: Suzuki S]]
[[Category: Tsutsumi N]]