Summary information and primary citation
- PDB-id
-
8r6w;
DSSR-derived features in text and
JSON formats; DNAproDB
- Class
- viral protein
- Method
- cryo-EM (3.35 Å)
- Summary
- Structure of the sftsv l protein in a
transcription-priming state with bound capped RNA
[transcription-priming]
- Reference
-
Williams HM, Thorkelsson SR, Vogel D, Busch C, Milewski
M, Cusack S, Grunewald K, Quemin ERJ, Rosenthal M (2024):
"Structural
snapshots of phenuivirus cap-snatching and
transcription." Nucleic Acids Res.,
52, 6049-6065. doi: 10.1093/nar/gkae330.
- Abstract
- Severe fever with thrombocytopenia syndrome virus
(SFTSV) is a human pathogen that is now endemic to several
East Asian countries. The viral large (L) protein catalyzes
viral transcription by stealing host mRNA caps via a
process known as cap-snatching. Here, we establish an in
vitro cap-snatching assay and present three high-quality
electron cryo-microscopy (cryo-EM) structures of the SFTSV
L protein in biologically relevant, transcription-specific
states. In a priming-state structure, we show capped RNA
bound to the L protein cap-binding domain (CBD). The L
protein conformation in this priming structure is
significantly different from published replication-state
structures, in particular the N- and C-terminal domains.
The capped-RNA is positioned in a way that it can feed
directly into the RNA-dependent RNA polymerase (RdRp) ready
for elongation. We also captured the L protein in an
early-elongation state following primer-incorporation
demonstrating that this priming conformation is retained at
least in the very early stages of primer extension. This
structural data is complemented by in vitro biochemical and
cell-based assays. Together, these insights further our
mechanistic understanding of how SFTSV and other
bunyaviruses incorporate stolen host mRNA fragments into
their viral transcripts thereby allowing the virus to
hijack host cell translation machinery.
