DNA-Packing Portal and Capsid-Associated Tegument Complexes in the Tumor Herpesvirus KSHV.

Capsid / metabolism Capsid Proteins / chemistry Cryoelectron Microscopy / methods DNA Packaging DNA, Viral / metabolism Genome, Viral Herpesvirus 8, Human / chemistry Humans Models, Molecular Sarcoma, Kaposi / virology Virus Assembly
Kaposi's sarcoma-associated herpesvirus capsid cryo-EM gammaherpesvirus genome herpesvirus microscopy portal tegument virology

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
05 09 2019
Historique:
received: 07 02 2019
revised: 16 05 2019
accepted: 17 07 2019
pubmed: 27 8 2019
medline: 17 6 2020
entrez: 27 8 2019
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.cell.2019.07.035 PMID: 31447177 PMC: PMC6753055
pubmed: 31447177
pii: S0092-8674(19)30834-7
doi: 10.1016/j.cell.2019.07.035
pmc: PMC6753055
mid: NIHMS1539076
pii:
doi:

Substances chimiques

Capsid Proteins 0
DNA, Viral 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1329-1343.e12

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI094386
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE023591
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE025567
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR023057
Pays : United States
Organisme : NIGMS NIH HHS
ID : U24 GM116792
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM071940
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE027901
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA177322
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA091791
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE028583
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Danyang Gong (D)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Xinghong Dai (X)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Jonathan Jih (J)

California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA 90095, USA.

Yun-Tao Liu (YT)

California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Integrative Imaging, Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China (USTC), Hefei, Anhui 230026, China.

Guo-Qiang Bi (GQ)

Center for Integrative Imaging, Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China (USTC), Hefei, Anhui 230026, China.

Ren Sun (R)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: rsun@mednet.ucla.edu.

Z Hong Zhou (ZH)

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: hong.zhou@ucla.edu.

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Classifications MeSH

questionsmedicales.fr › Structures virales › Virion › Nucléocapside › Capside › DNA-Packing Portal and Capsid-Associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines nucléocapside › Protéines de capside › DNA-Packing Portal and Capsid-Associated...
questionsmedicales.fr › Techniques d'investigation › Microscopie électronique › Cryomicroscopie électronique › DNA-Packing Portal and Capsid-Associated...
questionsmedicales.fr › Phénomènes génétiques › Empaquetage de l'ADN › DNA-Packing Portal and Capsid-Associated...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN viral › DNA-Packing Portal and Capsid-Associated...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Génome microbien › Génome viral › DNA-Packing Portal and Capsid-Associated...
questionsmedicales.fr › Virus › Virus oncogènes › Virus tumoraux à ADN › Gammaherpesvirinae › Rhadinovirus › Herpèsvirus humain de type 8 › DNA-Packing Portal and Capsid-Associated...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › DNA-Packing Portal and Capsid-Associated...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › DNA-Packing Portal and Capsid-Associated...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu vasculaire › Sarcome de Kaposi › DNA-Packing Portal and Capsid-Associated...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › Assemblage viral › DNA-Packing Portal and Capsid-Associated...