Summary information and primary citation
- PDB-id
-
3l25;
DSSR-derived features in text and
JSON formats
- Class
- RNA binding protein-RNA
- Method
- X-ray (2.0 Å)
- Summary
- Crystal structure of zaire ebola vp35 interferon
inhibitory domain bound to 8 bp dsrna
- Reference
-
Leung DW, Prins KC, Borek DM, Farahbakhsh M, Tufariello
JM, Ramanan P, Nix JC, Helgeson LA, Otwinowski Z,
Honzatko RB, Basler CF, Amarasinghe GK (2010): "Structural
basis for dsRNA recognition and interferon antagonism by
Ebola VP35." Nat.Struct.Mol.Biol.,
17, 165-172. doi: 10.1038/nsmb.1765.
- Abstract
- Ebola viral protein 35 (VP35), encoded by the highly
pathogenic Ebola virus, facilitates host immune evasion by
antagonizing antiviral signaling pathways, including those
initiated by RIG-I-like receptors. Here we report the
crystal structure of the Ebola VP35 interferon inhibitory
domain (IID) bound to short double-stranded RNA (dsRNA),
which together with in vivo results reveals how VP35-dsRNA
interactions contribute to immune evasion. Conserved basic
residues in VP35 IID recognize the dsRNA backbone, whereas
the dsRNA blunt ends are 'end-capped' by a pocket of
hydrophobic residues that mimic RIG-I-like receptor
recognition of blunt-end dsRNA. Residues critical for RNA
binding are also important for interferon inhibition in
vivo but not for viral polymerase cofactor function of
VP35. These results suggest that simultaneous recognition
of dsRNA backbone and blunt ends provides a mechanism by
which Ebola VP35 antagonizes host dsRNA sensors and immune
responses.
