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

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dc.contributor.authorFaustino, André F.
dc.contributor.authorSilva Martins, Ana
dc.contributor.authorKarguth, Nina
dc.contributor.authorArtilheiro, Vanessa
dc.contributor.authorEnguita, Francisco J.
dc.contributor.authorRicardo, Joana
dc.contributor.authorSantos, Nuno C.
dc.contributor.authorMartins, Ivo C.
dc.date.accessioned2022-04-28T16:24:59Z
dc.date.available2022-04-28T16:24:59Z
dc.date.issued2019
dc.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/).pt_PT
dc.description.abstractDengue, 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.pt_PT
dc.description.sponsorshipThis 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Mol Sci. 2019 Aug 8;20(16):3870pt_PT
dc.identifier.doi10.3390/ijms20163870pt_PT
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10451/52589
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationDENGUE VIRUS REPLICATION: THE INTERPLAY BETWEEN LIPID DROPLETS AND THE CAPSID PROTEIN
dc.relationA nanotechnology approach to Flavivirus-targeted drug development strategies
dc.relationMODELATION OF CALCITONIN AMYLOID FORMATIONBY LIPID MEMBRANES AND EXTRACELLULAR MATRIX
dc.relationA nanotechnology approach to Flavivirus-targeted drug development strategies
dc.relationNot Available
dc.relationInstituto de Medicina Molecular
dc.relation.publisherversionhttps://www.mdpi.com/journal/ijmspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectDengue virus (DENV)pt_PT
dc.subjectFlaviviruspt_PT
dc.subjectCapsid protein (C protein)pt_PT
dc.subjectCircular dichroismpt_PT
dc.subjectIntrinsically disordered protein (IDP)pt_PT
dc.subjectProtein–RNA interactionspt_PT
dc.subjectProtein–host lipid systems interactionpt_PT
dc.subjectTime-resolved fluorescence anisotropypt_PT
dc.titleStructural and functional properties of the capsid protein of Dengue and related Flaviviruspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDENGUE VIRUS REPLICATION: THE INTERPLAY BETWEEN LIPID DROPLETS AND THE CAPSID PROTEIN
oaire.awardTitleA nanotechnology approach to Flavivirus-targeted drug development strategies
oaire.awardTitleMODELATION OF CALCITONIN AMYLOID FORMATIONBY LIPID MEMBRANES AND EXTRACELLULAR MATRIX
oaire.awardTitleA nanotechnology approach to Flavivirus-targeted drug development strategies
oaire.awardTitleNot Available
oaire.awardTitleInstituto de Medicina Molecular
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-ENB%2F117013%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F77609%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F113698%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F95856%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00772%2F2013%2FCP1170%2FCT0004/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND%2F01670%2F2017%2FCP1396%2FCT0005/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIM%2F50005%2F2019/PT
oaire.citation.issue16pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume20pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamOE
oaire.fundingStreamInvestigador FCT
oaire.fundingStreamCEEC IND 2017
oaire.fundingStream6817 - DCRRNI ID
person.familyNameda Costa Faustino
person.familyNameSilva Martins
person.familyNameEnguita
person.familyNameRicardo
person.familyNameSantos
person.familyNameMartins
person.givenNameAndré Filipe
person.givenNameAna
person.givenNameFrancisco J.
person.givenNameJoana
person.givenNameNuno
person.givenNameIvo
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project.funder.identifierhttp://doi.org/10.13039/501100001871
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rcaap.typearticlept_PT
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