Structural and functional properties of the capsid protein of Dengue and related Flavivirus

Detalhes bibliográficos
Autor(a) principal: Faustino, André F.
Data de Publicação: 2019
Outros Autores: Silva Martins, Ana, Karguth, Nina, Artilheiro, Vanessa, Enguita, Francisco J., Ricardo, Joana, Santos, Nuno C., Martins, Ivo 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/10451/52589
Resumo: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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spelling Structural and functional properties of the capsid protein of Dengue and related FlavivirusDengue virus (DENV)FlavivirusCapsid protein (C protein)Circular dichroismIntrinsically disordered protein (IDP)Protein–RNA interactionsProtein–host lipid systems interactionTime-resolved fluorescence anisotropy© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Dengue, West Nile and Zika, closely related viruses of the Flaviviridae family, are an increasing global threat, due to the expansion of their mosquito vectors. They present a very similar viral particle with an outer lipid bilayer containing two viral proteins and, within it, the nucleocapsid core. This core is composed by the viral RNA complexed with multiple copies of the capsid protein, a crucial structural protein that mediates not only viral assembly, but also encapsidation, by interacting with host lipid systems. The capsid is a homodimeric protein that contains a disordered N-terminal region, an intermediate flexible fold section and a very stable conserved fold region. Since a better understanding of its structure can give light into its biological activity, here, first, we compared and analyzed relevant mosquito-borne Flavivirus capsid protein sequences and their predicted structures. Then, we studied the alternative conformations enabled by the N-terminal region. Finally, using dengue virus capsid protein as main model, we correlated the protein size, thermal stability and function with its structure/dynamics features. The findings suggest that the capsid protein interaction with host lipid systems leads to minor allosteric changes that may modulate the specific binding of the protein to the viral RNA. Such mechanism can be targeted in future drug development strategies, namely by using improved versions of pep14-23, a dengue virus capsid protein peptide inhibitor, previously developed by us. Such knowledge can yield promising advances against Zika, dengue and closely related Flavivirus.This work was supported by “Fundação para a Ciência e a Tecnologia–Ministério da Ciência, Tecnologia e Ensino Superior” (FCT-MCTES, Portugal) project PTDC/SAU-ENB/117013/2010, Calouste Gulbenkian Foundation (FCG, Portugal) project Science Frontiers Research Prize 2010. A.F.F., A.S.M. and J.C.R. also acknowledge FCT-MCTES fellowships SFRH/BD/77609/2011, PD/BD/113698/2015 and SFRH/BD/95856/2013, respectively. I.C.M. acknowledges FCT-MCTES Programs “Investigador FCT” (IF/00772/2013) and “Concurso de Estímulo ao Emprego Científico” (CEECIND/01670/2017). This work was also supported by UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/ Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado.MDPIRepositório da Universidade de LisboaFaustino, André F.Silva Martins, AnaKarguth, NinaArtilheiro, VanessaEnguita, Francisco J.Ricardo, JoanaSantos, Nuno C.Martins, Ivo C.2022-04-28T16:24:59Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/52589engInt J Mol Sci. 2019 Aug 8;20(16):38701661-659610.3390/ijms201638701422-0067info: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:RCAAP2023-11-08T16:57:52Zoai:repositorio.ul.pt:10451/52589Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:03:39.698165Repositório 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 Structural and functional properties of the capsid protein of Dengue and related Flavivirus
title Structural and functional properties of the capsid protein of Dengue and related Flavivirus
spellingShingle Structural and functional properties of the capsid protein of Dengue and related Flavivirus
Faustino, André F.
Dengue virus (DENV)
Flavivirus
Capsid protein (C protein)
Circular dichroism
Intrinsically disordered protein (IDP)
Protein–RNA interactions
Protein–host lipid systems interaction
Time-resolved fluorescence anisotropy
title_short Structural and functional properties of the capsid protein of Dengue and related Flavivirus
title_full Structural and functional properties of the capsid protein of Dengue and related Flavivirus
title_fullStr Structural and functional properties of the capsid protein of Dengue and related Flavivirus
title_full_unstemmed Structural and functional properties of the capsid protein of Dengue and related Flavivirus
title_sort Structural and functional properties of the capsid protein of Dengue and related Flavivirus
author Faustino, André F.
author_facet Faustino, André F.
Silva Martins, Ana
Karguth, Nina
Artilheiro, Vanessa
Enguita, Francisco J.
Ricardo, Joana
Santos, Nuno C.
Martins, Ivo C.
author_role author
author2 Silva Martins, Ana
Karguth, Nina
Artilheiro, Vanessa
Enguita, Francisco J.
Ricardo, Joana
Santos, Nuno C.
Martins, Ivo C.
author2_role author
author
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.
Silva Martins, Ana
Karguth, Nina
Artilheiro, Vanessa
Enguita, Francisco J.
Ricardo, Joana
Santos, Nuno C.
Martins, Ivo C.
dc.subject.por.fl_str_mv Dengue virus (DENV)
Flavivirus
Capsid protein (C protein)
Circular dichroism
Intrinsically disordered protein (IDP)
Protein–RNA interactions
Protein–host lipid systems interaction
Time-resolved fluorescence anisotropy
topic Dengue virus (DENV)
Flavivirus
Capsid protein (C protein)
Circular dichroism
Intrinsically disordered protein (IDP)
Protein–RNA interactions
Protein–host lipid systems interaction
Time-resolved fluorescence anisotropy
description © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01T00:00:00Z
2022-04-28T16:24:59Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/52589
url http://hdl.handle.net/10451/52589
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Int J Mol Sci. 2019 Aug 8;20(16):3870
1661-6596
10.3390/ijms20163870
1422-0067
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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