8tep
Human cytomegalovirus portal vertex, virion configuration 1 (VC1)
Structural highlights
FunctionLTP_HCMVA Large tegument protein that plays multiple roles in the viral cycle. During viral entry, remains associated with the capsid while most of the tegument is detached and participates in the capsid transport toward the host nucleus. Plays a role in the routing of the capsid at the nuclear pore complex and subsequent uncoating. Within the host nucleus, acts as a deneddylase and promotes the degradation of nuclear CRLs (cullin-RING ubiquitin ligases) and thereby stabilizes nuclear CRL substrates, while cytoplasmic CRLs remain unaffected. These modifications prevent host cell cycle S-phase progression and create a favorable environment allowing efficient viral genome replication. Participates later in the secondary envelopment of capsids. Indeed, plays a linker role for the association of the outer viral tegument to the capsids together with the inner tegument protein.[HAMAP-Rule:MF_04044] Publication Abstract from PubMedThe compartmentalization of eukaryotic cells presents considerable challenges to the herpesvirus life cycle. The herpesvirus tegument, a bulky proteinaceous aggregate sandwiched between herpesviruses' capsid and envelope, is uniquely evolved to address these challenges, yet tegument structure and organization remain poorly characterized. We use deep-learning-enhanced cryogenic electron microscopy to investigate the tegument of human cytomegalovirus virions and noninfectious enveloped particles (NIEPs; a genome packaging-aborted state), revealing a portal-biased tegumentation scheme. We resolve atomic structures of portal vertex-associated tegument (PVAT) and identify multiple configurations of PVAT arising from layered reorganization of pUL77, pUL48 (large tegument protein), and pUL47 (inner tegument protein) assemblies. Analyses show that pUL77 seals the last-packaged viral genome end through electrostatic interactions, pUL77 and pUL48 harbor a head-linker-capsid-binding motif conducive to PVAT reconfiguration, and pUL47/48 dimers form 45-nm-long filaments extending from the portal vertex. These results provide a structural framework for understanding how herpesvirus tegument facilitates and evolves during processes spanning viral genome packaging to delivery. The incredible bulk: Human cytomegalovirus tegument architectures uncovered by AI-empowered cryo-EM.,Jih J, Liu YT, Liu W, Zhou ZH Sci Adv. 2024 Feb 23;10(8):eadj1640. doi: 10.1126/sciadv.adj1640. Epub 2024 Feb , 23. PMID:38394211[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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