3l4q
From Proteopedia
Contents |
Structural insights into phosphoinositide 3-kinase activation by the influenza A virus NS1 protein
Template:ABSTRACT PUBMED 20133840
Function
[NS1_I34A1] 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). [P85B_BOVIN] Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane.
About this Structure
3l4q is a 4 chain structure with sequence from Bovin and I34a1. Full crystallographic information is available from OCA.
See Also
Reference
- Hale BG, Kerry PS, Jackson D, Precious BL, Gray A, Killip MJ, Randall RE, Russell RJ. Structural insights into phosphoinositide 3-kinase activation by the influenza A virus NS1 protein. Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1954-9. Epub 2010 Jan 19. PMID:20133840 doi:10.1073/pnas.0910715107
