In:
PLOS Computational Biology, Public Library of Science (PLoS), Vol. 18, No. 5 ( 2022-5-12), p. e1010121-
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.
Type of Medium:
Online Resource
ISSN:
1553-7358
DOI:
10.1371/journal.pcbi.1010121
DOI:
10.1371/journal.pcbi.1010121.g001
DOI:
10.1371/journal.pcbi.1010121.g002
DOI:
10.1371/journal.pcbi.1010121.g003
DOI:
10.1371/journal.pcbi.1010121.g004
DOI:
10.1371/journal.pcbi.1010121.g005
DOI:
10.1371/journal.pcbi.1010121.g006
DOI:
10.1371/journal.pcbi.1010121.g007
DOI:
10.1371/journal.pcbi.1010121.s001
DOI:
10.1371/journal.pcbi.1010121.s002
DOI:
10.1371/journal.pcbi.1010121.s003
DOI:
10.1371/journal.pcbi.1010121.s004
DOI:
10.1371/journal.pcbi.1010121.s005
DOI:
10.1371/journal.pcbi.1010121.s006
DOI:
10.1371/journal.pcbi.1010121.s007
DOI:
10.1371/journal.pcbi.1010121.s008
DOI:
10.1371/journal.pcbi.1010121.s009
DOI:
10.1371/journal.pcbi.1010121.s010
DOI:
10.1371/journal.pcbi.1010121.s011
DOI:
10.1371/journal.pcbi.1010121.s012
DOI:
10.1371/journal.pcbi.1010121.s013
DOI:
10.1371/journal.pcbi.1010121.s014
DOI:
10.1371/journal.pcbi.1010121.s015
DOI:
10.1371/journal.pcbi.1010121.r001
DOI:
10.1371/journal.pcbi.1010121.r002
DOI:
10.1371/journal.pcbi.1010121.r003
DOI:
10.1371/journal.pcbi.1010121.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2193340-6