Summary information and primary citation
- PDB-id
-
7krn;
DSSR-derived features in text and
JSON formats
- Class
- transferase-hydrolase-RNA
- Method
- cryo-EM (3.4 Å)
- Summary
- Structure of sars-cov-2 backtracked complex bound to
nsp13 helicase - nsp13(1)-btc
- Reference
-
Malone B, Chen J, Wang Q, Llewellyn E, Choi YJ, Olinares
PDB, Cao X, Hernandez C, Eng ET, Chait BT, Shaw DE,
Landick R, Darst SA, Campbell EA (2021): "Structural
basis for backtracking by the SARS-CoV-2
replication-transcription complex."
Proc.Natl.Acad.Sci.USA, 118.
doi: 10.1073/pnas.2102516118.
- Abstract
- 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.
