Summary information and primary citation
- PDB-id
-
8gzq;
DSSR-derived features in text and
JSON formats
- Class
- viral protein
- Method
- cryo-EM (3.9 Å)
- Summary
- cryo-EM structure of the ns5-ns3-sla complex
- Reference
-
Osawa T, Aoki M, Ehara H, Sekine SI (2023): "Structures
of dengue virus RNA replicase complexes."
Mol.Cell, 83, 2781. doi:
10.1016/j.molcel.2023.06.023.
- Abstract
- Dengue is a mosquito-borne viral infection caused by
dengue virus (DENV), a member of the flaviviruses. The DENV
genome is a 5'-capped positive-sense RNA with a unique
5'-stem-loop structure (SLA), which is essential for RNA
replication and 5' capping. The virus-encoded proteins NS5
and NS3 are responsible for viral genome replication, but
the structural basis by which they cooperatively conduct
the required tasks has remained unclear. Here, we report
the cryoelectron microscopy (cryo-EM) structures of
SLA-bound NS5 (PC), NS3-bound PC (PC-NS3), and an
RNA-elongating NS5-NS3 complex (EC). While SLA bridges the
NS5 methyltransferase and RNA-dependent RNA polymerase
domains in PC, the NS3 helicase domain displaces it in
elongation complex (EC). The SLA- and NS3-binding sites
overlap with that of human STAT2. These structures
illuminate the key steps in DENV genome replication,
namely, SLA-dependent replication initiation, processive
RNA elongation, and 5' capping of the nascent genomic RNA,
thereby providing foundations to combat flaviviruses.
