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TitleDNA-Packing Portal and Capsid-Associated Tegument Complexes in the Tumor Herpesvirus KSHV.
Journal, issue, pagesCell, Vol. 178, Issue 6, Page 1329-1343.e12, Year 2019
Publish dateSep 5, 2019
AuthorsDanyang Gong / Xinghong Dai / Jonathan Jih / Yun-Tao Liu / Guo-Qiang Bi / Ren Sun / Z Hong Zhou /
PubMed AbstractAssembly of Kaposi's sarcoma-associated herpesvirus (KSHV) begins at a bacteriophage-like portal complex that nucleates formation of an icosahedral capsid with capsid-associated tegument complexes ...Assembly of Kaposi's sarcoma-associated herpesvirus (KSHV) begins at a bacteriophage-like portal complex that nucleates formation of an icosahedral capsid with capsid-associated tegument complexes (CATCs) and facilitates translocation of an ∼150-kb dsDNA genome, followed by acquisition of a pleomorphic tegument and envelope. Because of deviation from icosahedral symmetry, KSHV portal and tegument structures have largely been obscured in previous studies. Using symmetry-relaxed cryo-EM, we determined the in situ structure of the KSHV portal and its interactions with surrounding capsid proteins, CATCs, and the terminal end of KSHV's dsDNA genome. Our atomic models of the portal and capsid/CATC, together with visualization of CATCs' variable occupancy and alternate orientation of CATC-interacting vertex triplexes, suggest a mechanism whereby the portal orchestrates procapsid formation and asymmetric long-range determination of CATC attachment during DNA packaging prior to pleomorphic tegumentation/envelopment. Structure-based mutageneses confirm that a triplex deep binding groove for CATCs is a hotspot that holds promise for antiviral development.
External linksPubMed:31447177 / Publisher's page
KeywordsCapsid / Capsid Proteins / Cryoelectron Microscopy / DNA Packaging / DNA, Viral / Genome, Viral / Herpesvirus 8, Human / Humans / Models, Molecular / Sarcoma, Kaposi / Virus Assembly / VIRAL PROTEIN / genome / portal / genome packaging / VIRUS / tegument / vertex / complex
MethodsEM (single particle)
Resolution3.7 - 7.6 A
Structure data

EMDB-20430:
Kaposi's sarcoma-associated herpesvirus (KSHV), C1 virion capsid reconstruction

EMDB-20431:
Kaposi's sarcoma-associated herpesvirus (KSHV), C1 portal vertex reconstruction

EMDB-20432:
Kaposi's sarcoma-associated herpesvirus (KSHV), C5 portal vertex structure

EMDB-20433:
Kaposi's sarcoma-associated herpesvirus (KSHV), C1 penton vertex register, CATC-absent structure

EMDB-20436:
Kaposi's sarcoma-associated herpesvirus (KSHV), C1 penton vertex register, CATC-binding structure

EMDB-20437:
Kaposi's sarcoma-associated herpesvirus (KSHV), C12 portal dodecamer structure

PDB-6ppb:
Kaposi's sarcoma-associated herpesvirus (KSHV), C5 portal vertex structure

PDB-6ppd:
Kaposi's sarcoma-associated herpesvirus (KSHV), C1 penton vertex register, CATC-absent structure

PDB-6pph:
Kaposi's sarcoma-associated herpesvirus (KSHV), C1 penton vertex register, CATC-binding structure

PDB-6ppi:
Kaposi's sarcoma-associated herpesvirus (KSHV), C12 portal dodecamer structure

Source
  • Human gammaherpesvirus 8
  • HHV-8 (virus)
  • human herpesvirus 8

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