Crystal structure of the NS1 effector domain W182A mutant from influenza A/Vietnam/1203/2004 (H5N1) virusCrystal structure of the NS1 effector domain W182A mutant from influenza A/Vietnam/1203/2004 (H5N1) virus

Structural highlights

3p38 is a 3 chain structure with sequence from Influenza A virus (A/environment/Viet Nam/1203/2004(H5N1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.76Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

D1LP63_9INFA 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).[SAAS:SAAS00210185] 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).[SAAS:SAAS00210196]

See Also

3p38, resolution 2.76Å

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