Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain.

JC virus is a member of the Polyomavirus family of DNA tumor viruses and the causative agent of progressive multifocal leukoencephalopathy (PML). PML is a disease that occurs primarily in people who are immunocompromised and is usually fatal. As with other Polyomavirus family members, the replicatio...

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Autores principales:	Gretchen Meinke, Paul J Phelan, Radha Kalekar, Jong Shin, Jacques Archambault, Andrew Bohm, Peter A Bullock
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7e4b30b6762a45c09e6e596efe3849e3
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spelling	oai:doaj.org-article:7e4b30b6762a45c09e6e596efe3849e32021-11-18T06:06:57ZInsights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain.1553-73661553-737410.1371/journal.ppat.1003966https://doaj.org/article/7e4b30b6762a45c09e6e596efe3849e32014-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586168/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374JC virus is a member of the Polyomavirus family of DNA tumor viruses and the causative agent of progressive multifocal leukoencephalopathy (PML). PML is a disease that occurs primarily in people who are immunocompromised and is usually fatal. As with other Polyomavirus family members, the replication of JC virus (JCV) DNA is dependent upon the virally encoded protein T-antigen. To further our understanding of JCV replication, we have determined the crystal structure of the origin-binding domain (OBD) of JCV T-antigen. This structure provides the first molecular understanding of JCV T-ag replication functions; for example, it suggests how the JCV T-ag OBD site-specifically binds to the major groove of GAGGC sequences in the origin. Furthermore, these studies suggest how the JCV OBDs interact during subsequent oligomerization events. We also report that the OBD contains a novel "pocket"; which sequesters the A1 & B2 loops of neighboring molecules. Mutagenesis of a residue in the pocket associated with the JCV T-ag OBD interfered with viral replication. Finally, we report that relative to the SV40 OBD, the surface of the JCV OBD contains one hemisphere that is highly conserved and one that is highly variable.Gretchen MeinkePaul J PhelanRadha KalekarJong ShinJacques ArchambaultAndrew BohmPeter A BullockPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 2, p e1003966 (2014)
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 Gretchen Meinke Paul J Phelan Radha Kalekar Jong Shin Jacques Archambault Andrew Bohm Peter A Bullock Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain.
description	JC virus is a member of the Polyomavirus family of DNA tumor viruses and the causative agent of progressive multifocal leukoencephalopathy (PML). PML is a disease that occurs primarily in people who are immunocompromised and is usually fatal. As with other Polyomavirus family members, the replication of JC virus (JCV) DNA is dependent upon the virally encoded protein T-antigen. To further our understanding of JCV replication, we have determined the crystal structure of the origin-binding domain (OBD) of JCV T-antigen. This structure provides the first molecular understanding of JCV T-ag replication functions; for example, it suggests how the JCV T-ag OBD site-specifically binds to the major groove of GAGGC sequences in the origin. Furthermore, these studies suggest how the JCV OBDs interact during subsequent oligomerization events. We also report that the OBD contains a novel "pocket"; which sequesters the A1 & B2 loops of neighboring molecules. Mutagenesis of a residue in the pocket associated with the JCV T-ag OBD interfered with viral replication. Finally, we report that relative to the SV40 OBD, the surface of the JCV OBD contains one hemisphere that is highly conserved and one that is highly variable.
format	article
author	Gretchen Meinke Paul J Phelan Radha Kalekar Jong Shin Jacques Archambault Andrew Bohm Peter A Bullock
author_facet	Gretchen Meinke Paul J Phelan Radha Kalekar Jong Shin Jacques Archambault Andrew Bohm Peter A Bullock
author_sort	Gretchen Meinke
title	Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain.
title_short	Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain.
title_full	Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain.
title_fullStr	Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain.
title_full_unstemmed	Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain.
title_sort	insights into the initiation of jc virus dna replication derived from the crystal structure of the t-antigen origin binding domain.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/7e4b30b6762a45c09e6e596efe3849e3
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Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain.

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