Self-assembly of dengue virus empty capsid-like particles in solution

dc.contributor.authorNeves-Martins, Thais C.
dc.contributor.authorMebus-Antunes, Nathane C.
dc.contributor.authorNeto, Carlos H.G.
dc.contributor.authorBarbosa, Glauce M.
dc.contributor.authorAlmeida, Fabio C.L.
dc.contributor.authorCaruso, Icaro P. [UNESP]
dc.contributor.authorDa Poian, Andrea T.
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2023-07-29T13:44:00Z
dc.date.available2023-07-29T13:44:00Z
dc.date.issued2023-03-17
dc.description.abstractNucleocapsid (NC) assembly is an essential step of the virus replication cycle. It ensures genome protection and transmission among hosts. Flaviviruses are human viruses for which envelope structure is well known, whereas no information on NC organization is available. Here we designed a dengue virus capsid protein (DENVC) mutant in which a highly positive spot conferred by arginine 85 in α4-helix was replaced by a cysteine residue, simultaneously removing the positive charge and restricting the intermolecular motion through the formation of a disulfide cross-link. We showed that the mutant self-assembles into capsid-like particles (CLP) in solution without nucleic acids. Using biophysical techniques, we investigated capsid assembly thermodynamics, showing that an efficient assembly is related to an increased DENVC stability due to α4/α4′ motion restriction. To our knowledge, this is the first time that flaviviruses’ empty capsid assembly is obtained in solution, revealing the R85C mutant as a powerful tool to understand the NC assembly mechanism.en
dc.description.affiliationInstituto de Bioquímica Médica Leopoldo de Meis Universidade Federal do Rio de Janeiro, Rio de Janeiro
dc.description.affiliationCentro Nacional de Biologia Estrutural e Bioimagem Universidade Federal do Rio de Janeiro, Rio de Janeiro
dc.description.affiliationCentro Multiusuário de Inovação Biomolecular e Departamento de Física Instituto de Biociências Letras e Ciências Exatas Universidade Estadual de São Paulo, São Paulo
dc.description.affiliationUnespCentro Multiusuário de Inovação Biomolecular e Departamento de Física Instituto de Biociências Letras e Ciências Exatas Universidade Estadual de São Paulo, São Paulo
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPERJ: 204.432/2014
dc.description.sponsorshipIdFAPERJ: 239.229/2018
dc.description.sponsorshipIdCNPq: 312650/2021-3
dc.description.sponsorshipIdCNPq: 439306/2018-3
dc.description.sponsorshipIdFAPERJ: E-26/201.173/2021
dc.description.sponsorshipIdFAPERJ: E-26/201.316/2016
dc.identifierhttp://dx.doi.org/10.1016/j.isci.2023.106197
dc.identifier.citationiScience, v. 26, n. 3, 2023.
dc.identifier.doi10.1016/j.isci.2023.106197
dc.identifier.issn2589-0042
dc.identifier.scopus2-s2.0-85149073058
dc.identifier.urihttp://hdl.handle.net/11449/248435
dc.language.isoeng
dc.relation.ispartofiScience
dc.sourceScopus
dc.subjectBiological sciences
dc.subjectMolecular biology
dc.subjectMolecular mechanism of behavior
dc.subjectVirology
dc.titleSelf-assembly of dengue virus empty capsid-like particles in solutionen
dc.typeArtigo

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