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TitleThe incredible bulk: Human cytomegalovirus tegument architectures uncovered by AI-empowered cryo-EM.
Journal, issue, pagesSci Adv, Vol. 10, Issue 8, Page eadj1640, Year 2024
Publish dateFeb 23, 2024
AuthorsJonathan Jih / Yun-Tao Liu / Wei Liu / Z Hong Zhou /
PubMed AbstractThe compartmentalization of eukaryotic cells presents considerable challenges to the herpesvirus life cycle. The herpesvirus tegument, a bulky proteinaceous aggregate sandwiched between ...The 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.
External linksSci Adv / PubMed:38394211 / PubMed Central
MethodsEM (single particle)
Resolution3.02 - 10.88 Å
Structure data

EMDB-41194, PDB-8tep:
Human cytomegalovirus portal vertex, virion configuration 1 (VC1)
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-41200, PDB-8tes:
Human cytomegalovirus portal vertex, virion configuration 2 (VC2)
Method: EM (single particle) / Resolution: 3.27 Å

EMDB-41201, PDB-8tet:
Human cytomegalovirus portal vertex, non-infectious enveloped particle (NIEP) configuration 1 (NC1)
Method: EM (single particle) / Resolution: 4.26 Å

EMDB-41202, PDB-8teu:
Human cytomegalovirus portal vertex, non-infectious enveloped particle (NIEP) configuration 2 - inverted (NC2-inv)
Method: EM (single particle) / Resolution: 4.01 Å

EMDB-41204, PDB-8tew:
Human cytomegalovirus penton vertex, CVSC-bound configuration
Method: EM (single particle) / Resolution: 3.02 Å

EMDB-41206: Human cytomegalovirus portal vertex, non-infectious enveloped particle (NIEP) configuration 2 (NC2)
Method: EM (single particle) / Resolution: 4.29 Å

EMDB-41213: Human cytomegalovirus portal vertex-resolved capsid, virion configuration 1 (VC1)
Method: EM (single particle) / Resolution: 10.88 Å

EMDB-41214: Human cytomegalovirus portal vertex-resolved capsid, virion configuration 2 (VC2)
Method: EM (single particle) / Resolution: 10.88 Å

EMDB-41215: Human cytomegalovirus portal vertex-resolved capsid, non-infectious enveloped particle (NIEP) configuration 1 (NC1)
Method: EM (single particle) / Resolution: 6.44 Å

EMDB-41216: Human cytomegalovirus portal vertex-resolved capsid, non-infectious enveloped particle (NIEP) configuration 2 - inverted (NC2-inv)
Method: EM (single particle) / Resolution: 6.44 Å

Source
  • human herpesvirus 5 strain ad169
KeywordsVIRUS / tegument / portal / DNA packaging / intracellular transport / penton / CVSC

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