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

dc.contributor.authorCaruso, Icaro Putinhon [UNESP]
dc.contributor.authordos Santos Almeida, Vitor
dc.contributor.authordo Amaral, Mariana Juliani
dc.contributor.authorde Andrade, Guilherme Caldas
dc.contributor.authorde Araújo, Gabriela Rocha
dc.contributor.authorde Araújo, Talita Stelling
dc.contributor.authorde Azevedo, Jéssica Moreira
dc.contributor.authorBarbosa, Glauce Moreno
dc.contributor.authorBartkevihi, Leonardo
dc.contributor.authorBezerra, Peter Reis
dc.contributor.authordos Santos Cabral, Katia Maria
dc.contributor.authorde Lourenço, Isabella Otênio [UNESP]
dc.contributor.authorMalizia-Motta, Clara L.F.
dc.contributor.authorde Luna Marques, Aline
dc.contributor.authorMebus-Antunes, Nathane Cunha
dc.contributor.authorNeves-Martins, Thais Cristtina
dc.contributor.authorde Sá, Jéssica Maróstica [UNESP]
dc.contributor.authorSanches, Karoline [UNESP]
dc.contributor.authorSantana-Silva, Marcos Caique
dc.contributor.authorVasconcelos, Ariana Azevedo
dc.contributor.authorda Silva Almeida, Marcius
dc.contributor.authorde Amorim, Gisele Cardoso
dc.contributor.authorAnobom, Cristiane Dinis
dc.contributor.authorDa Poian, Andrea T.
dc.contributor.authorGomes-Neto, Francisco
dc.contributor.authorPinheiro, Anderson S.
dc.contributor.authorAlmeida, Fabio C.L.
dc.contributor.institutionFederal University of Rio de Janeiro
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionMultidisciplinary Center for Research in Biology (NUMPEX)
dc.contributor.institutionOswaldo Cruz Foundation (FIOCRUZ)
dc.contributor.institutionRio BioNMR Network
dc.date.accessioned2022-04-28T19:50:20Z
dc.date.available2022-04-28T19:50:20Z
dc.date.issued2022-04-01
dc.description.abstractThe 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.en
dc.description.affiliationInstitute of Medical Biochemistry Federal University of Rio de Janeiro
dc.description.affiliationMultiuser Center for Biomolecular Innovation (CMIB) Department of Physics São Paulo State University (UNESP)
dc.description.affiliationNational Center of Nuclear Magnetic Resonance (CNRMN) CENABIO Federal University of Rio de Janeiro
dc.description.affiliationFaculty of Pharmacy Federal University of Rio de Janeiro
dc.description.affiliationProtein Advanced Biochemistry (PAB) CENABIO Federal University of Rio de Janeiro
dc.description.affiliationDepartment of Biochemistry Institute of Chemistry Federal University of Rio de Janeiro
dc.description.affiliationMultidisciplinary Center for Research in Biology (NUMPEX) Campus Duque de Caxias Federal University of Rio de Janeiro
dc.description.affiliationLaboratory of Toxinology Oswaldo Cruz Foundation (FIOCRUZ)
dc.description.affiliationRio BioNMR Network
dc.description.affiliationUnespMultiuser Center for Biomolecular Innovation (CMIB) Department of Physics São Paulo State University (UNESP)
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: 202.279/2018
dc.description.sponsorshipIdFAPERJ: 204.432/2014
dc.description.sponsorshipIdFAPERJ: 210.361/2015
dc.description.sponsorshipIdFAPERJ: 239.229/2018
dc.description.sponsorshipIdFAPERJ: 255.940/2020
dc.description.sponsorshipIdCNPq: 309564/2017-4
dc.description.sponsorshipIdCNPq: 439306/2018-3
dc.format.extent466-480
dc.identifierhttp://dx.doi.org/10.1016/j.ijbiomac.2022.01.121
dc.identifier.citationInternational Journal of Biological Macromolecules, v. 203, p. 466-480.
dc.identifier.doi10.1016/j.ijbiomac.2022.01.121
dc.identifier.issn1879-0003
dc.identifier.issn0141-8130
dc.identifier.scopus2-s2.0-85123929571
dc.identifier.urihttp://hdl.handle.net/11449/223395
dc.language.isoeng
dc.relation.ispartofInternational Journal of Biological Macromolecules
dc.sourceScopus
dc.subjectBinding specificity
dc.subjectDNA/RNA binding protein
dc.subjectSARS-CoV-2 nucleocapsid protein
dc.titleInsights into the specificity for the interaction of the promiscuous SARS-CoV-2 nucleocapsid protein N-terminal domain with deoxyribonucleic acidsen
dc.typeArtigo

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