Insights into the specificity for the interaction of the promiscuous SARS-CoV-2 nucleocapsid protein N-terminal domain with deoxyribonucleic acids

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Autor(es): dc.contributorFederal University of Rio de Janeiro-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorMultidisciplinary Center for Research in Biology (NUMPEX)-
Autor(es): dc.contributorOswaldo Cruz Foundation (FIOCRUZ)-
Autor(es): dc.contributorRio BioNMR Network-
Autor(es): dc.creatorCaruso, Icaro Putinhon-
Autor(es): dc.creatordos Santos Almeida, Vitor-
Autor(es): dc.creatordo Amaral, Mariana Juliani-
Autor(es): dc.creatorde Andrade, Guilherme Caldas-
Autor(es): dc.creatorde Araújo, Gabriela Rocha-
Autor(es): dc.creatorde Araújo, Talita Stelling-
Autor(es): dc.creatorde Azevedo, Jéssica Moreira-
Autor(es): dc.creatorBarbosa, Glauce Moreno-
Autor(es): dc.creatorBartkevihi, Leonardo-
Autor(es): dc.creatorBezerra, Peter Reis-
Autor(es): dc.creatordos Santos Cabral, Katia Maria-
Autor(es): dc.creatorde Lourenço, Isabella Otênio-
Autor(es): dc.creatorMalizia-Motta, Clara L.F.-
Autor(es): dc.creatorde Luna Marques, Aline-
Autor(es): dc.creatorMebus-Antunes, Nathane Cunha-
Autor(es): dc.creatorNeves-Martins, Thais Cristtina-
Autor(es): dc.creatorde Sá, Jéssica Maróstica-
Autor(es): dc.creatorSanches, Karoline-
Autor(es): dc.creatorSantana-Silva, Marcos Caique-
Autor(es): dc.creatorVasconcelos, Ariana Azevedo-
Autor(es): dc.creatorda Silva Almeida, Marcius-
Autor(es): dc.creatorde Amorim, Gisele Cardoso-
Autor(es): dc.creatorAnobom, Cristiane Dinis-
Autor(es): dc.creatorDa Poian, Andrea T.-
Autor(es): dc.creatorGomes-Neto, Francisco-
Autor(es): dc.creatorPinheiro, Anderson S.-
Autor(es): dc.creatorAlmeida, Fabio C.L.-
Data de aceite: dc.date.accessioned2025-08-21T22:21:53Z-
Data de disponibilização: dc.date.available2025-08-21T22:21:53Z-
Data de envio: dc.date.issued2022-04-28-
Data de envio: dc.date.issued2022-04-28-
Data de envio: dc.date.issued2022-04-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.ijbiomac.2022.01.121-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/223395-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/223395-
Descrição: dc.descriptionThe SARS-CoV-2 nucleocapsid protein (N) is a multifunctional promiscuous nucleic acid-binding protein, which plays a major role in nucleocapsid assembly and discontinuous RNA transcription, facilitating the template switch of transcriptional regulatory sequences (TRS). Here, we dissect the structural features of the N protein N-terminal domain (N-NTD) and N-NTD plus the SR-rich motif (N-NTD-SR) upon binding to single and double-stranded TRS DNA, as well as their activities for dsTRS melting and TRS-induced liquid-liquid phase separation (LLPS). Our study gives insights on the specificity for N-NTD(-SR) interaction with TRS. We observed an approximation of the triple-thymidine (TTT) motif of the TRS to β-sheet II, giving rise to an orientation difference of ~25° between dsTRS and non-specific sequence (dsNS). It led to a local unfavorable energetic contribution that might trigger the melting activity. The thermodynamic parameters of binding of ssTRSs and dsTRS suggested that the duplex dissociation of the dsTRS in the binding cleft is entropically favorable. We showed a preference for TRS in the formation of liquid condensates when compared to NS. Moreover, our results on DNA binding may serve as a starting point for the design of inhibitors, including aptamers, against N, a possible therapeutic target essential for the virus infectivity.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionInstitute of Medical Biochemistry Federal University of Rio de Janeiro-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation (CMIB) Department of Physics São Paulo State University (UNESP)-
Descrição: dc.descriptionNational Center of Nuclear Magnetic Resonance (CNRMN) CENABIO Federal University of Rio de Janeiro-
Descrição: dc.descriptionFaculty of Pharmacy Federal University of Rio de Janeiro-
Descrição: dc.descriptionProtein Advanced Biochemistry (PAB) CENABIO Federal University of Rio de Janeiro-
Descrição: dc.descriptionDepartment of Biochemistry Institute of Chemistry Federal University of Rio de Janeiro-
Descrição: dc.descriptionMultidisciplinary Center for Research in Biology (NUMPEX) Campus Duque de Caxias Federal University of Rio de Janeiro-
Descrição: dc.descriptionLaboratory of Toxinology Oswaldo Cruz Foundation (FIOCRUZ)-
Descrição: dc.descriptionRio BioNMR Network-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation (CMIB) Department of Physics São Paulo State University (UNESP)-
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-
Descrição: dc.descriptionCNPq: 309564/2017-4-
Descrição: dc.descriptionCNPq: 439306/2018-3-
Formato: dc.format466-480-
Idioma: dc.languageen-
Relação: dc.relationInternational Journal of Biological Macromolecules-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectBinding specificity-
Palavras-chave: dc.subjectDNA/RNA binding protein-
Palavras-chave: dc.subjectSARS-CoV-2 nucleocapsid protein-
Título: dc.titleInsights into the specificity for the interaction of the promiscuous SARS-CoV-2 nucleocapsid protein N-terminal domain with deoxyribonucleic acids-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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