Structural domains of SARS-CoV-2 nucleocapsid protein coordinate to compact long nucleic acid substrates.
Nucleic Acids Res
; 51(1): 290-303, 2023 01 11.
Article
in English
| MEDLINE | ID: covidwho-2189413
ABSTRACT
The SARS-CoV-2 nucleocapsid (N) protein performs several functions including binding, compacting, and packaging the â¼30 kb viral genome into the viral particle. N protein consists of two ordered domains, with the N terminal domain (NTD) primarily associated with RNA binding and the C terminal domain (CTD) primarily associated with dimerization/oligomerization, and three intrinsically disordered regions, an N-arm, a C-tail, and a linker that connects the NTD and CTD. We utilize an optical tweezers system to isolate a long single-stranded nucleic acid substrate to measure directly the binding and packaging function of N protein at a single molecule level in real time. We find that N protein binds the nucleic acid substrate with high affinity before oligomerizing and forming a highly compact structure. By comparing the activities of truncated protein variants missing the NTD, CTD, and/or linker, we attribute specific steps in this process to the structural domains of N protein, with the NTD driving initial binding to the substrate and ensuring high localized protein density that triggers interprotein interactions mediated by the CTD, which forms a compact and stable protein-nucleic acid complex suitable for packaging into the virion.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA, Viral
/
Coronavirus Nucleocapsid Proteins
/
SARS-CoV-2
/
COVID-19
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Nucleic Acids Res
Year:
2023
Document Type:
Article
Affiliation country:
Nar
Similar
MEDLINE
...
LILACS
LIS