7RE3

SARS-CoV-2 replication-transcription complex bound to nsp13 helicase - nsp13(2)-RTC dimer

7RE3 の概要

• エントリーDOI: 10.2210/pdb7re3/pdb
• EMDBエントリー: 24432
• 分子名称: RNA-directed RNA polymerase, ALUMINUM FLUORIDE, CHAPSO, ... (11 entities in total)
• 機能のキーワード: rna-dependent rna polymerase, viral replication-transcription complex, transcription, viral proteins, replication-transcription complex, replication/transcription
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 653397.17

構造登録者

Chen, J.,Malone, B.,Campbell, E.A.,Darst, S.A. (登録日: 2021-07-12, 公開日: 2021-11-24, 最終更新日: 2024-06-05)

主引用文献

Chen, J.,Wang, Q.,Malone, B.,Llewellyn, E.,Pechersky, Y.,Maruthi, K.,Eng, E.T.,Perry, J.K.,Campbell, E.A.,Shaw, D.E.,Darst, S.A.
Ensemble cryo-EM reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex.
Nat.Struct.Mol.Biol., 29:250-260, 2022

PubMed Abstract: The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA-dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex or RTC) associated with two copies of nsp13 (nsp13-RTC). One copy of nsp13 interacts with the template-RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backward on the RNA template (backtracking), prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of nsp13. Here we use cryogenic-electron microscopy and molecular dynamics simulations to analyze the nsp13-RTC, revealing four distinct conformational states of the helicases. The results indicate a mechanism for the nsp13-RTC to turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis or backtracking in response to stimuli at the RdRp active site.

PubMed: 35260847
DOI: 10.1038/s41594-022-00734-6

実験手法

ELECTRON MICROSCOPY (3.33 Å)