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Matsuda, A.* ; Plewka, J.* ; Rawski, M.* ; Mourao, A. ; Zajko, W.* ; Siebenmorgen, T. ; Kresik, L.* ; Lis, K.* ; Jones, A. ; Pachota, M.* ; Karim, A.* ; Hartman, K.* ; Nirwal, S.* ; Sonani, R.* ; Chykunova, Y.* ; Minia, I.* ; Mak, P.* ; Landthaler, M.* ; Nowotny, M.* ; Dubin, G.* ; Sattler, M. ; Suder, P.* ; Popowicz, G.M. ; Pyrc, K.* ; Czarna, A.*

Despite the odds: Formation of the SARS-CoV-2 methylation complex.

Nucleic Acids Res. 52, 6441-6458 (2024)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Structural Basis; Protein; Exoribonuclease; Replication; Reveals; Nsp14; Domain
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Quellenangaben Band: 52, Heft: 11, Seiten: 6441-6458 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Great Clarendon St, Oxford Ox2 6dp, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Förderungen Jagiellonian University in Krakow