Structural dynamics of SARS-CoV-2 nucleocapsid protein induced by RNA binding.
PLoS Comput Biol
; 18(5): e1010121, 2022 05.
Article
in English
| MEDLINE | ID: covidwho-1846916
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Coronavirus Nucleocapsid Proteins
/
SARS-CoV-2
Limits:
Humans
Language:
English
Journal:
PLoS Comput Biol
Journal subject:
Biology
/
Medical Informatics
Year:
2022
Document Type:
Article
Affiliation country:
Journal.pcbi.1010121
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