KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/51126 |
Resumo: | © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
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KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Latency-associated nuclear antigen (LANA) is central to episomal tethering, replication and transcriptional regulation of γ2-herpesviruses. LANA binds cooperatively to the terminal repeat (TR) region of the viral episome via adjacent LANA binding sites (LBS), but the molecular mechanism by which LANA assembles on the TR remains elusive. We show that KSHV LANA and MHV-68 LANA proteins bind LBS DNA using strikingly different modes. Solution structure of LANA complexes revealed that while kLANA tetramer is intrinsically bent both in the free and bound state to LBS1-2 DNA, mLANA oligomers instead adopt a rigid linear conformation. In addition, we report a novel non-ring kLANA structure that displays more flexibility at its assembly interface than previously demonstrated. We identified a hydrophobic pivot point located at the dimer-dimer assembly interface, which gives rotational freedom for kLANA to adopt variable conformations to accommodate both LBS1-2 and LBS2-1-3 DNA. Alterations in the arrangement of LBS within TR or at the tetramer assembly interface have a drastic effect on the ability of kLANA binding. We also show kLANA and mLANA DNA binding functions can be reciprocated. Although KSHV and MHV-68 are closely related, the findings provide new insights into how the structure, oligomerization, and DNA binding of LANA have evolved differently to assemble on the TR DNA.Fundação para a Ciência e a Tecnologia (FCT) Investigator Grant [IF/01023/2013 to C.E.M.]; Harvard Medical School Portugal Program in Translational Research and Information [HMSP-ICT/0021/2010 to J.P.S., C.E.M., M.A.C. and K.M.K.]; National Cancer Institute/National Institutes of Health (NCI/NIH) [CA082036 to KMK]; National Institutes of Dental and Craniofacial Research/National Institutes of Health (NIDCR/NIH) [DE025208 to K.M.K.]; European Community's Seventh Framework Programme (FP7/2007–2013) under BioStruct-X [283570]. This work was also supported by Instruct, part of the European Strategy Forum on Research Infrastructures (ESFRI) and through national member agreements. Funding for open access charges: FCT.Oxford University PressRepositório da Universidade de LisboaPonnusamy, RajeshPetoukhov, Maxim V.Correia, BrunoCustodio, Tania F.Juillard, FrancelineTan, MinPires de Miranda, MartaCarrondo, Maria A.Simas, J PedroKaye, Kenneth M.Svergun, Dmitri I.McVey, Colin E.2022-02-04T15:28:02Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/51126engNucleic Acids Res. 2015 Nov 16;43(20):10039-100540305-104810.1093/nar/gkv9871362-4962info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:55:38Zoai:repositorio.ul.pt:10451/51126Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:26.770626Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA |
| title |
KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA |
| spellingShingle |
KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA Ponnusamy, Rajesh |
| title_short |
KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA |
| title_full |
KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA |
| title_fullStr |
KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA |
| title_full_unstemmed |
KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA |
| title_sort |
KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA |
| author |
Ponnusamy, Rajesh |
| author_facet |
Ponnusamy, Rajesh Petoukhov, Maxim V. Correia, Bruno Custodio, Tania F. Juillard, Franceline Tan, Min Pires de Miranda, Marta Carrondo, Maria A. Simas, J Pedro Kaye, Kenneth M. Svergun, Dmitri I. McVey, Colin E. |
| author_role |
author |
| author2 |
Petoukhov, Maxim V. Correia, Bruno Custodio, Tania F. Juillard, Franceline Tan, Min Pires de Miranda, Marta Carrondo, Maria A. Simas, J Pedro Kaye, Kenneth M. Svergun, Dmitri I. McVey, Colin E. |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Ponnusamy, Rajesh Petoukhov, Maxim V. Correia, Bruno Custodio, Tania F. Juillard, Franceline Tan, Min Pires de Miranda, Marta Carrondo, Maria A. Simas, J Pedro Kaye, Kenneth M. Svergun, Dmitri I. McVey, Colin E. |
| description |
© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z 2022-02-04T15:28:02Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/51126 |
| url |
http://hdl.handle.net/10451/51126 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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Nucleic Acids Res. 2015 Nov 16;43(20):10039-10054 0305-1048 10.1093/nar/gkv987 1362-4962 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Oxford University Press |
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Oxford University Press |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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