Structural dynamics of SARS-CoV-2 nucleocapsid protein induced by RNA binding.

Autor: Ribeiro-Filho HV; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Jara GE; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Batista FAH; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Schleder GR; Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Costa Tonoli CC; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Soprano AS; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Guimarães SL; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Borges AC; Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Cassago A; Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Bajgelman MC; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Marques RE; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Trivella DBB; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Franchini KG; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Figueira ACM; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Benedetti CE; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil., Lopes-de-Oliveira PS; Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil.
Jazyk: angličtina
Zdroj: PLoS computational biology [PLoS Comput Biol] 2022 May 12; Vol. 18 (5), pp. e1010121. Date of Electronic Publication: 2022 May 12 (Print Publication: 2022).
DOI: 10.1371/journal.pcbi.1010121
Abstrakt: The nucleocapsid (N) protein of the SARS-CoV-2 virus, the causal agent of COVID-19, is a multifunction phosphoprotein that plays critical roles in the virus life cycle, including transcription and packaging of the viral RNA. To play such diverse roles, the N protein has two globular RNA-binding modules, the N- (NTD) and C-terminal (CTD) domains, which are connected by an intrinsically disordered region. Despite the wealth of structural data available for the isolated NTD and CTD, how these domains are arranged in the full-length protein and how the oligomerization of N influences its RNA-binding activity remains largely unclear. Herein, using experimental data from electron microscopy and biochemical/biophysical techniques combined with molecular modeling and molecular dynamics simulations, we show that, in the absence of RNA, the N protein formed structurally dynamic dimers, with the NTD and CTD arranged in extended conformations. However, in the presence of RNA, the N protein assumed a more compact conformation where the NTD and CTD are packed together. We also provided an octameric model for the full-length N bound to RNA that is consistent with electron microscopy images of the N protein in the presence of RNA. Together, our results shed new light on the dynamics and higher-order oligomeric structure of this versatile protein.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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