In:
Molecular Biomedicine, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2023-05-22)
Kurzfassung:
SARS-CoV-2 and its variants, with the Omicron subvariant XBB currently prevailing the global infections, continue to pose threats on public health worldwide. This non-segmented positive-stranded RNA virus encodes the multi-functional nucleocapsid protein (N) that plays key roles in viral infection, replication, genome packaging and budding. N protein consists of two structural domains, NTD and CTD, and three intrinsically disordered regions (IDRs) including the N IDR , the serine/arginine rich motif (SR IDR ), and the C IDR . Previous studies revealed functions of N protein in RNA binding, oligomerization, and liquid–liquid phase separation (LLPS), however, characterizations of individual domains and their dissected contributions to N protein functions remain incomplete. In particular, little is known about N protein assembly that may play essential roles in viral replication and genome packing. Here, we present a modular approach to dissect functional roles of individual domains in SARS-CoV-2 N protein that reveals inhibitory or augmented modulations of protein assembly and LLPS in the presence of viral RNAs. Intriguingly, full-length N protein (N FL ) assembles into ring-like architecture whereas the truncated SR IDR -CTD-C IDR (N 182-419 ) promotes filamentous assembly. Moreover, LLPS droplets of N FL and N 182-419 are significantly enlarged in the presence of viral RNAs, and we observed filamentous structures in the N 182-419 droplets using correlative light and electron microscopy (CLEM), suggesting that the formation of LLPS droplets may promote higher-order assembly of N protein for transcription, replication and packaging. Together this study expands our understanding of the multiple functions of N protein in SARS-CoV-2.
Materialart:
Online-Ressource
ISSN:
2662-8651
DOI:
10.1186/s43556-023-00129-z
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2023
ZDB Id:
3033856-6
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