Dynamics of the SARS-CoV-2 nucleoprotein N-terminal domain triggers RNA duplex destabilization

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorInstitute of Medical Biochemistry Leopoldo de Meis and National Center for Structural Biology and Bioimaging-
Autor(es): dc.contributorFederal University of Rio de Janeiro-
Autor(es): dc.creatorCaruso, Ícaro P.-
Autor(es): dc.creatorSanches, Karoline-
Autor(es): dc.creatorDa Poian, Andrea T.-
Autor(es): dc.creatorPinheiro, Anderson S.-
Autor(es): dc.creatorAlmeida, Fabio C.L.-
Data de aceite: dc.date.accessioned2025-08-21T16:24:23Z-
Data de disponibilização: dc.date.available2025-08-21T16:24:23Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2021-07-20-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.bpj.2021.06.003-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/229128-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/229128-
Descrição: dc.descriptionThe nucleocapsid (N) protein of betacoronaviruses is responsible for nucleocapsid assembly and other essential regulatory functions. The N protein N-terminal domain (N-NTD) interacts and melts the double-stranded transcriptional regulatory sequences (dsTRSs), regulating the discontinuous subgenome transcription process. Here, we used molecular dynamics (MD) simulations to study the binding of the severe acute respiratory syndrome coronavirus 2 N-NTD to nonspecific (NS) and TRS dsRNAs. We probed dsRNAs’ Watson-Crick basepairing over 25 replicas of 100 ns MD simulations, showing that only one N-NTD of dimeric N is enough to destabilize dsRNAs, triggering melting initiation. dsRNA destabilization driven by N-NTD was more efficient for dsTRSs than dsNS. N-NTD dynamics, especially a tweezer-like motion of β2-β3 and Δ2-β5 loops, seems to play a key role in Watson-Crick basepairing destabilization. Based on experimental information available in the literature, we constructed kinetics models for N-NTD-mediated dsRNA melting. Our results support a 1:1 stoichiometry (N-NTD/dsRNA), matching MD simulations and raising different possibilities for N-NTD action: 1) two N-NTD arms of dimeric N would bind to two different RNA sites, either closely or spatially spaced in the viral genome, in a cooperative manner; and 2) monomeric N-NTD would be active, opening up the possibility of a regulatory dissociation event.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation and Department of Physics Institute of Biosciences Letters and Exact Sciences São Paulo State University (UNESP), São José do Rio Preto-
Descrição: dc.descriptionInstitute of Medical Biochemistry Leopoldo de Meis and National Center for Structural Biology and Bioimaging-
Descrição: dc.descriptionDepartment of Biochemistry Institute of Chemistry Federal University of Rio de Janeiro-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation and Department of Physics Institute of Biosciences Letters and Exact Sciences São Paulo State University (UNESP), São José do Rio Preto-
Descrição: dc.descriptionFAPERJ: 202.279/2018-
Descrição: dc.descriptionFAPERJ: 204.432/2014-
Descrição: dc.descriptionFAPERJ: 210.361/2015-
Descrição: dc.descriptionFAPERJ: 239.229/2018-
Descrição: dc.descriptionFAPERJ: 255.940/2020-
Formato: dc.format2814-2827-
Idioma: dc.languageen-
Relação: dc.relationBiophysical Journal-
???dc.source???: dc.sourceScopus-
Título: dc.titleDynamics of the SARS-CoV-2 nucleoprotein N-terminal domain triggers RNA duplex destabilization-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

Não existem arquivos associados a este item.