SARS-CoV-2 variants preferentially emerge at intrinsically disordered protein sites helping immune evasion.
FEBS J
; 289(14): 4240-4250, 2022 07.
Article
in English
| MEDLINE | ID: covidwho-1666305
ABSTRACT
The SARS-CoV-2 pandemic is maintained by the emergence of successive variants, highlighting the flexibility of the protein sequences of the virus. We show that experimentally determined intrinsically disordered regions (IDRs) are abundant in the SARS-CoV-2 viral proteins, making up to 28% of disorder content for the S1 subunit of spike and up to 51% for the nucleoprotein, with the vast majority of mutations occurring in the 13 major variants mapped to these IDRs. Strikingly, antigenic sites are enriched in IDRs, in the receptor-binding domain (RBD) and in the N-terminal domain (NTD), suggesting a key role of structural flexibility in the antigenicity of the SARS-CoV-2 protein surface. Mutations occurring in the S1 subunit and nucleoprotein (N) IDRs are critical for immune evasion and antibody escape, suggesting potential additional implications for vaccines and monoclonal therapeutic strategies. Overall, this suggests the presence of variable regions on S1 and N protein surfaces, which confer sequence and antigenic flexibility to the virus without altering its protein functions.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Intrinsically Disordered Proteins
/
COVID-19
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Journal:
FEBS J
Journal subject:
Biochemistry
Year:
2022
Document Type:
Article
Affiliation country:
Febs.16379
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