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| Title | Activation of cytomegalovirus-encoded G protein-coupled receptor UL33 by an innate N-terminal peptide. |
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| Journal, issue, pages | Commun Biol, Year 2026 |
| Publish date | Feb 12, 2026 |
 Authors | Anna K Drzazga / Shota Suzuki / Caroline Wouters / Felix Faas / Kouki Nishikawa / Akiko Kamegawa / Yoshinori Fujiyoshi / Mette M Rosenkilde / Naotaka Tsutsumi /   |
| PubMed Abstract | 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 ...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 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. |
 External links | Commun Biol / PubMed:41680497 |
| Methods | EM (single particle) |
| Resolution | 3.3 Å |
| Structure data | EMDB-65918, PDB-9wey: |
| Source |
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 Keywords | MEMBRANE PROTEIN / HCMV / viral protein / viral-host interaction / GPCR |
homo sapiens (human)
lama glama (llama)
human betaherpesvirus 5