Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.

Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.

Latency-associated nuclear antigen (LANA) mediates γ2-herpesvirus genome persistence and regulates transcription. We describe the crystal structure of the murine gammaherpesvirus-68 LANA C-terminal domain at 2.2 Å resolution. The structure reveals an alpha-beta fold that assembles as a dimer, remini...

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Autores principales: Bruno Correia, Sofia A Cerqueira, Chantal Beauchemin, Marta Pires de Miranda, Shijun Li, Rajesh Ponnusamy, Lénia Rodrigues, Thomas R Schneider, Maria A Carrondo, Kenneth M Kaye, J Pedro Simas, Colin E McVey
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
Materias:
Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Acceso en línea:https://doaj.org/article/e9ab2330f422454c8330e6d4aa52cb19
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spelling oai:doaj.org-article:e9ab2330f422454c8330e6d4aa52cb192021-11-18T06:07:28ZCrystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.1553-73661553-737410.1371/journal.ppat.1003673https://doaj.org/article/e9ab2330f422454c8330e6d4aa52cb192013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24146618/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Latency-associated nuclear antigen (LANA) mediates γ2-herpesvirus genome persistence and regulates transcription. We describe the crystal structure of the murine gammaherpesvirus-68 LANA C-terminal domain at 2.2 Å resolution. The structure reveals an alpha-beta fold that assembles as a dimer, reminiscent of Epstein-Barr virus EBNA1. A predicted DNA binding surface is present and opposite this interface is a positive electrostatic patch. Targeted DNA recognition substitutions eliminated DNA binding, while certain charged patch mutations reduced bromodomain protein, BRD4, binding. Virus containing LANA abolished for DNA binding was incapable of viable latent infection in mice. Virus with mutations at the charged patch periphery exhibited substantial deficiency in expansion of latent infection, while central region substitutions had little effect. This deficiency was independent of BRD4. These results elucidate the LANA DNA binding domain structure and reveal a unique charged region that exerts a critical role in viral latent infection, likely acting through a host cell protein(s).Bruno CorreiaSofia A CerqueiraChantal BeaucheminMarta Pires de MirandaShijun LiRajesh PonnusamyLénia RodriguesThomas R SchneiderMaria A CarrondoKenneth M KayeJ Pedro SimasColin E McVeyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 10, p e1003673 (2013)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Bruno Correia
Sofia A Cerqueira
Chantal Beauchemin
Marta Pires de Miranda
Shijun Li
Rajesh Ponnusamy
Lénia Rodrigues
Thomas R Schneider
Maria A Carrondo
Kenneth M Kaye
J Pedro Simas
Colin E McVey
Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.
description Latency-associated nuclear antigen (LANA) mediates γ2-herpesvirus genome persistence and regulates transcription. We describe the crystal structure of the murine gammaherpesvirus-68 LANA C-terminal domain at 2.2 Å resolution. The structure reveals an alpha-beta fold that assembles as a dimer, reminiscent of Epstein-Barr virus EBNA1. A predicted DNA binding surface is present and opposite this interface is a positive electrostatic patch. Targeted DNA recognition substitutions eliminated DNA binding, while certain charged patch mutations reduced bromodomain protein, BRD4, binding. Virus containing LANA abolished for DNA binding was incapable of viable latent infection in mice. Virus with mutations at the charged patch periphery exhibited substantial deficiency in expansion of latent infection, while central region substitutions had little effect. This deficiency was independent of BRD4. These results elucidate the LANA DNA binding domain structure and reveal a unique charged region that exerts a critical role in viral latent infection, likely acting through a host cell protein(s).
format article
author Bruno Correia
Sofia A Cerqueira
Chantal Beauchemin
Marta Pires de Miranda
Shijun Li
Rajesh Ponnusamy
Lénia Rodrigues
Thomas R Schneider
Maria A Carrondo
Kenneth M Kaye
J Pedro Simas
Colin E McVey
author_facet Bruno Correia
Sofia A Cerqueira
Chantal Beauchemin
Marta Pires de Miranda
Shijun Li
Rajesh Ponnusamy
Lénia Rodrigues
Thomas R Schneider
Maria A Carrondo
Kenneth M Kaye
J Pedro Simas
Colin E McVey
author_sort Bruno Correia
title Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.
title_short Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.
title_full Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.
title_fullStr Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.
title_full_unstemmed Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.
title_sort crystal structure of the gamma-2 herpesvirus lana dna binding domain identifies charged surface residues which impact viral latency.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/e9ab2330f422454c8330e6d4aa52cb19
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