A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2'-O methylation of its first nucleotide.
Nat Commun
; 12(1): 3287, 2021 06 02.
Article
en En
| MEDLINE
| ID: mdl-34078893
ABSTRACT
The SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2'-OH of the first transcribed nucleotide of the viral mRNA by covalently attaching a methyl group to it. The 2'-O methylation of the first nucleotide converts the status of mRNA cap from Cap-0 to Cap-1, and thus, helps the virus evade immune surveillance in host cells. Here, we report two structures of nsp16/nsp10 representing pre- and post-release states of the RNA product (Cap-1). We observe overall widening of the enzyme upon product formation, and an inward twisting motion in the substrate binding region upon product release. These conformational changes reset the enzyme for the next round of catalysis. The structures also identify a unique binding mode and the importance of a divalent metal ion for 2'-O methylation. We also describe underlying structural basis for the perturbed enzymatic activity of a clinical variant of SARS-CoV-2, and a previous SARS-CoV outbreak strain.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Caperuzas de ARN
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ARN Viral
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Proteínas no Estructurales Virales
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Proteínas Reguladoras y Accesorias Virales
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SARS-CoV-2
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Magnesio
Idioma:
En
Año:
2021
Tipo del documento:
Article