Structural highlights
Function
[NS1_I76A2] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism (By similarity). Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (By similarity).
Publication Abstract from PubMed
Influenza A virus NS1 protein is a multifunctional virulence factor. Here, we report a crystal structure for the NS1 effector domain of avian influenza virus A/Duck/Albany/76. Comparison of this structure with that reported for a human strain shows both proteins share a common monomer conformation, albeit with subtle differences. Strikingly, our data reveal a novel helix-helix dimeric interface between monomers of the avian NS1 protein, which is also found in the human NS1 crystal lattice. We re-evaluate the current model of NS1 dimeric assembly, and provide biochemical evidence to show tryptophan-187 (a residue located at the helix-helix interface) is essential for dimerization of this effector domain.
Structure of an avian influenza A virus NS1 protein effector domain.,Hale BG, Barclay WS, Randall RE, Russell RJ Virology. 2008 Aug 15;378(1):1-5. Epub 2008 Jun 27. PMID:18585749[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hale BG, Barclay WS, Randall RE, Russell RJ. Structure of an avian influenza A virus NS1 protein effector domain. Virology. 2008 Aug 15;378(1):1-5. Epub 2008 Jun 27. PMID:18585749 doi:http://dx.doi.org/S0042-6822(08)00364-4
