3l28
From Proteopedia
Crystal structure of Zaire Ebola VP35 interferon inhibitory domain K339A mutant
Structural highlights
FunctionVP35_EBOZM Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.[1] [2] [3] [4] [5] Publication Abstract from PubMedEbola 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. Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35.,Leung DW, Prins KC, Borek DM, Farahbakhsh M, Tufariello JM, Ramanan P, Nix JC, Helgeson LA, Otwinowski Z, Honzatko RB, Basler CF, Amarasinghe GK Nat Struct Mol Biol. 2010 Feb;17(2):165-72. Epub 2010 Jan 17. PMID:20081868[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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