Crystal structures of the SARS-CoV-2 nucleocapsid protein C-terminal domain and development of nucleocapsid-targeting nanobodies.
FEBS J
; 289(13): 3813-3825, 2022 07.
Article
in English
| MEDLINE | ID: covidwho-1476183
ABSTRACT
The ongoing outbreak of COVID-19 caused by SARS-CoV-2 has resulted in a serious public health threat globally. Nucleocapsid protein is a major structural protein of SARS-CoV-2 that plays important roles in the viral RNA packing, replication, assembly, and infection. Here, we report two crystal structures of nucleocapsid protein C-terminal domain (CTD) at resolutions of 2.0 Å and 3.1 Å, respectively. These two structures, crystallized under different conditions, contain 2 and 12 CTDs in asymmetric unit, respectively. Interestingly, despite different crystal packing, both structures show a similar dimeric form as the smallest unit, consistent with its solution form measured by the size-exclusion chromatography, suggesting an important role of CTD in the dimerization of nucleocapsid proteins. By analyzing the surface charge distribution, we identified a stretch of positively charged residues between Lys257 and Arg262 that are involved in RNA-binding. Through screening a single-domain antibodies (sdAbs) library, we identified four sdAbs targeting different regions of nucleocapsid protein with high affinities that have future potential to be used in viral detection and therapeutic purposes.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Single-Domain Antibodies
/
Coronavirus Nucleocapsid Proteins
Type of study:
Diagnostic study
Language:
English
Journal:
FEBS J
Journal subject:
Biochemistry
Year:
2022
Document Type:
Article
Affiliation country:
Febs.16239
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