Understanding dengue virus capsid protein interaction with key biological targets

Detalhes bibliográficos
Autor(a) principal: Faustino, André F.
Data de Publicação: 2015
Outros Autores: Martins, Ivo C., Carvalho, Filomena A., Castanho, Miguel A. R. B., Maurer-Stroh, Sebastian, Santos, Nuno C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/23504
Resumo: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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spelling Understanding dengue virus capsid protein interaction with key biological targetsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Supplementary information accompanies this paper at http://www.nature.com/srepDengue virus (DENV) causes over 500,000 hospitalizations and 20,000 deaths worldwide every year. Dengue epidemics now reach temperate regions due to globalization of trade and travel and climate changes. Currently, there are no successful therapeutic or preventive approaches. We previously developed a peptide drug lead, pep14-23, that inhibits the biologically relevant interaction of DENV capsid (C) protein with lipid droplets (LDs). Surprisingly, pep14-23 also inhibits DENV C interaction with very low-density lipoproteins (VLDL). We thus investigated the similarity between the proposed DENV C molecular targets in LDs and VLDL, respectively, the proteins perilipin 3 (PLIN3) and apolipoprotein E (APOE). APOE N-terminal and PLIN3 C-terminal regions are remarkably similar, namely APOE α -helix 4 (APOEα 4) and PLIN3 α -helix 5 (PLIN3α 5) sequences, which are also highly superimposable structurally. Interestingly, APOE α -helical N-terminal sequence and structure superimposes with DENV C α -helices α 1 and α 2. Moreover, the DENV C hydrophobic cleft can accommodate the structurally analogous APOEα 4 and PLIN3α 5 helical regions. Mirroring DENV C-LDs interaction (previously shown experimentally to require PLIN3), we experimentally demonstrated that DENV C-VLDL interaction requires APOE. Thus, the results fit well with previous data and suggest future drug development strategies targeting the above mentioned α –helical structures.We acknowledge the support of Fundação para a Ciência e Tecnologia – Ministério da Educação e Ciência (FCT-MEC, Portugal) project PTDC/SAU-ENB/117013/2010, and Calouste Gulbenkian Foundation (Portugal). AFF and ICM also acknowledge FCT-MEC fellowship SFRH/BD/77609/2011 and Investigador FCT Program research contract IF/00772/2013, respectively.Nature Publishing GroupRepositório da Universidade de LisboaFaustino, André F.Martins, Ivo C.Carvalho, Filomena A.Castanho, Miguel A. R. B.Maurer-Stroh, SebastianSantos, Nuno C.2016-04-21T13:11:58Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/23504engSci. Rep. 5, 105922045-232210.1038/srep10592info: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:RCAAP2023-11-08T16:11:33Zoai:repositorio.ul.pt:10451/23504Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:40:50.078129Repositório 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 Understanding dengue virus capsid protein interaction with key biological targets
title Understanding dengue virus capsid protein interaction with key biological targets
spellingShingle Understanding dengue virus capsid protein interaction with key biological targets
Faustino, André F.
title_short Understanding dengue virus capsid protein interaction with key biological targets
title_full Understanding dengue virus capsid protein interaction with key biological targets
title_fullStr Understanding dengue virus capsid protein interaction with key biological targets
title_full_unstemmed Understanding dengue virus capsid protein interaction with key biological targets
title_sort Understanding dengue virus capsid protein interaction with key biological targets
author Faustino, André F.
author_facet Faustino, André F.
Martins, Ivo C.
Carvalho, Filomena A.
Castanho, Miguel A. R. B.
Maurer-Stroh, Sebastian
Santos, Nuno C.
author_role author
author2 Martins, Ivo C.
Carvalho, Filomena A.
Castanho, Miguel A. R. B.
Maurer-Stroh, Sebastian
Santos, Nuno C.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Faustino, André F.
Martins, Ivo C.
Carvalho, Filomena A.
Castanho, Miguel A. R. B.
Maurer-Stroh, Sebastian
Santos, Nuno C.
description This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-01T00:00:00Z
2016-04-21T13:11:58Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/23504
url http://hdl.handle.net/10451/23504
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Sci. Rep. 5, 10592
2045-2322
10.1038/srep10592
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dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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