9wey

Structure of HCMV UL33 in complex with human Gs protein

spinqualitylabelsall models 9wey, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9wey is a 5 chain structure with sequence from Homo sapiens, Human betaherpesvirus 5 and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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). 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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