7R2V

Structure of nsp14 from SARS-CoV-2 in complex with SAH

7R2V の概要

• エントリーDOI: 10.2210/pdb7r2v/pdb
• 分子名称: Proofreading exoribonuclease nsp14, S-ADENOSYL-L-HOMOCYSTEINE, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• 機能のキーワード: nsp14, complex, sah, sars-cov-2, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 120617.99

構造登録者

Czarna, A.,Plewka, J.,Kresik, L.,Matsuda, A.,Abdulkarim, K.,Robinson, C.,OByrne, S.,Cunningham, F.,Georgiou, I.,Pachota, M.,Popowicz, G.M.,Wyatt, P.G.,Dubin, G.,Pyrc, K. (登録日: 2022-02-06, 公開日: 2022-03-09, 最終更新日: 2025-12-10)

主引用文献

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.,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

PubMed Abstract: 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.

PubMed: 35609600
DOI: 10.1016/j.str.2022.04.014

実験手法

X-RAY DIFFRACTION (2.53 Å)