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Despite the odds: formation of the SARS-CoV-2 methylation complex

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Item Type:Article
Title:Despite the odds: formation of the SARS-CoV-2 methylation complex
Creators Name:Matsuda, A. and Plewka, J. and Rawski, M. and Mourão, A. and Zajko, W. and Siebenmorgen, T. and Kresik, L. and Lis, K. and Jones, A.N. and Pachota, M. and Karim, A. and Hartman, K. and Nirwal, S. and Sonani, R. and Chykunova, Y. and Minia, I. and Mak, P. and Landthaler, M. and Nowotny, M. and Dubin, G. and Sattler, M. and Suder, P. and Popowicz, G.M. and Pyrć, K. and Czarna, A.
Abstract:Coronaviruses modify their single-stranded RNA genome with a methylated cap during replication to mimic the eukaryotic mRNAs. The capping process is initiated by several nonstructural proteins (nsp) encoded in the viral genome. The methylation is performed by two methyltransferases, nsp14 and nsp16, while nsp10 acts as a co-factor to both. Additionally, nsp14 carries an exonuclease domain which operates in the proofreading system during RNA replication of the viral genome. Both nsp14 and nsp16 were reported to independently bind nsp10, but the available structural information suggests that the concomitant interaction between these three proteins would be impossible due to steric clashes. Here, we show that nsp14, nsp10, and nsp16 can form a heterotrimer complex upon significant allosteric change. This interaction is expected to encourage the formation of mature capped viral mRNA, modulating nsp14's exonuclease activity, and protecting the viral RNA. Our findings show that nsp14 is amenable to allosteric regulation and may serve as a novel target for therapeutic approaches.
Source:Nucleic Acids Research
Publisher:Oxford University Press
Page Range:gkae165
Date:18 March 2024
Official Publication:https://doi.org/10.1093/nar/gkae165
PubMed:View item in PubMed
Related to:
https://edoc.mdc-berlin.de/21315/Preprint version

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