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Czarna, A.* ; Plewka, J.* ; Kresik, L.* ; Matsuda, A.* ; Karim, A.* ; Robinson, C.* ; O'Byrne, S.* ; Cunningham, F.* ; Georgiou, I.* ; Wilk, P.* ; Pachota, M.* ; Popowicz, G.M. ; Wyatt, P.G.* ; Dubin, G.* ; Pyrc, K.*

Refolding of lid subdomain of SARS-CoV-2 nsp14 upon nsp10 interaction releases exonuclease activity.

Structure 30, 1050-1054.e2 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
During RNA replication, coronaviruses require proofreading to maintain the integrity of their large genomes. Nsp14 associates with viral polymerase complex to excise the mismatched nucleotides. Aside from the exonuclease activity, nsp14 methyltransferase domain mediates cap methylation, facilitating translation initiation and protecting viral RNA from recognition by the innate immune sensors. The nsp14 exonuclease activity is modulated by a protein co-factor nsp10. While the nsp10/nsp14 complex structure is available, the mechanistic basis for nsp10-mediated modulation remains unclear in the absence of the nsp14 structure. Here, we provide a crystal structure of nsp14 in an apo-form. Comparative analysis of the apo- and nsp10-bound structures explain the modulatory role of the co-factor protein and reveal the allosteric nsp14 control mechanism essential for drug discovery. Further, the flexibility of the N-terminal lid of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nsp14 structure presented in this study rationalizes the recently proposed idea of nsp14/nsp10/nsp16 ternary complex.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Sah ; Sars-cov-2 ; Xrd ; Coronavirus ; Methylation ; Methyltransferase ; Nsp10 ; Nsp14 ; Proof-reading ; Structure
ISSN (print) / ISBN 0969-2126
e-ISSN 1878-4186
Zeitschrift Structure
Quellenangaben Band: 30, Heft: 8, Seiten: 1050-1054.e2 Artikelnummer: , Supplement: ,
Verlag Cell Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)