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A metal ion orients mRNA to ensure accurate 2’-O ribosyl methylation of the first nucleotide of the SARS-CoV-2 genome
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 su...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cold Spring Harbor Laboratory
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987004/ https://www.ncbi.nlm.nih.gov/pubmed/33758845 http://dx.doi.org/10.1101/2021.03.12.435174 |
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author | Viswanathan, Thiruselvam Misra, Anurag Chan, Siu-Hong Qi, Shan Dai, Nan Arya, Shailee Martinez-Sobrido, Luis Gupta, Yogesh K. |
author_facet | Viswanathan, Thiruselvam Misra, Anurag Chan, Siu-Hong Qi, Shan Dai, Nan Arya, Shailee Martinez-Sobrido, Luis Gupta, Yogesh K. |
author_sort | Viswanathan, Thiruselvam |
collection | PubMed |
description | 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 the host cell. 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. |
format | Online Article Text |
id | pubmed-7987004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-79870042021-03-24 A metal ion orients mRNA to ensure accurate 2’-O ribosyl methylation of the first nucleotide of the SARS-CoV-2 genome Viswanathan, Thiruselvam Misra, Anurag Chan, Siu-Hong Qi, Shan Dai, Nan Arya, Shailee Martinez-Sobrido, Luis Gupta, Yogesh K. bioRxiv Article 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 the host cell. 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. Cold Spring Harbor Laboratory 2021-03-12 /pmc/articles/PMC7987004/ /pubmed/33758845 http://dx.doi.org/10.1101/2021.03.12.435174 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Viswanathan, Thiruselvam Misra, Anurag Chan, Siu-Hong Qi, Shan Dai, Nan Arya, Shailee Martinez-Sobrido, Luis Gupta, Yogesh K. A metal ion orients mRNA to ensure accurate 2’-O ribosyl methylation of the first nucleotide of the SARS-CoV-2 genome |
title | A metal ion orients mRNA to ensure accurate 2’-O ribosyl methylation of the first nucleotide of the SARS-CoV-2 genome |
title_full | A metal ion orients mRNA to ensure accurate 2’-O ribosyl methylation of the first nucleotide of the SARS-CoV-2 genome |
title_fullStr | A metal ion orients mRNA to ensure accurate 2’-O ribosyl methylation of the first nucleotide of the SARS-CoV-2 genome |
title_full_unstemmed | A metal ion orients mRNA to ensure accurate 2’-O ribosyl methylation of the first nucleotide of the SARS-CoV-2 genome |
title_short | A metal ion orients mRNA to ensure accurate 2’-O ribosyl methylation of the first nucleotide of the SARS-CoV-2 genome |
title_sort | metal ion orients mrna to ensure accurate 2’-o ribosyl methylation of the first nucleotide of the sars-cov-2 genome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987004/ https://www.ncbi.nlm.nih.gov/pubmed/33758845 http://dx.doi.org/10.1101/2021.03.12.435174 |
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