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Structure paper

タイトル	Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 118, Issue 19, Year 2021
掲載日	2021年5月11日
著者	Brandon Malone / James Chen / Qi Wang / Eliza Llewellyn / Young Joo Choi / Paul Dominic B Olinares / Xinyun Cao / Carolina Hernandez / Edward T Eng / Brian T Chait / David E Shaw / Robert Landick / Seth A Darst / Elizabeth A Campbell /
PubMed 要旨	Backtracking, the reverse motion of the transcriptase enzyme on the nucleic acid template, is a universal regulatory feature of transcription in cellular organisms but its role in viruses is not ...Backtracking, the reverse motion of the transcriptase enzyme on the nucleic acid template, is a universal regulatory feature of transcription in cellular organisms but its role in viruses is not established. Here we present evidence that backtracking extends into the viral realm, where backtracking by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) may aid viral transcription and replication. Structures of SARS-CoV-2 RdRp bound to the essential nsp13 helicase and RNA suggested the helicase facilitates backtracking. We use cryo-electron microscopy, RNA-protein cross-linking, and unbiased molecular dynamics simulations to characterize SARS-CoV-2 RdRp backtracking. The results establish that the single-stranded 3' segment of the product RNA generated by backtracking extrudes through the RdRp nucleoside triphosphate (NTP) entry tunnel, that a mismatched nucleotide at the product RNA 3' end frays and enters the NTP entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking. Backtracking may aid proofreading, a crucial process for SARS-CoV-2 resistance against antivirals.
リンク	Proc Natl Acad Sci U S A / PubMed:33883267 / PubMed Central
手法	EM (単粒子)
解像度	3.2 - 3.6 Å
構造データ	23007 7krn EMDB-23007, PDB-7krn: Structure of SARS-CoV-2 backtracked complex bound to nsp13 helicase - nsp13(1)-BTC 手法: EM (単粒子) / 解像度: 3.4 Å 23008 7kro EMDB-23008, PDB-7kro: Structure of SARS-CoV-2 backtracked complex complex bound to nsp13 helicase - nsp13(2)-BTC 手法: EM (単粒子) / 解像度: 3.6 Å 23009 7krp EMDB-23009, PDB-7krp: Structure of SARS-CoV-2 backtracked complex complex bound to nsp13 helicase - BTC (local refinement) 手法: EM (単粒子) / 解像度: 3.2 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM / アデノシン二リン酸 ChemComp-1N7: CHAPSO / CHAPSO / 可溶化剤YM / CHAPS detergent ChemComp-AF3: ALUMINUM FLUORIDE / トリフルオロアルミニウム / フッ化アルミニウム
由来	severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2)
キーワード	TRANSFERASE/HYDROLASE/RNA / RNA-dependent RNA polymerase (RNA依存性RNAポリメラーゼ) / viral replication-transcription complex / transcription (転写 (生物学)) / viral proteins (ウイルスタンパク質) / TRANSFERASE-HYDROLASE-RNA complex / TRANSFERASE/RNA / TRANSFERASE-RNA complex