6nu0 | pdb_00006nu0
Solution NMR structure of 1918 NS1 effector domain
Structural highlights
Function[A0A2Z5CYV0_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. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. 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.[RuleBase:RU362113][SAAS:SAAS01036581] 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 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.[RuleBase:RU362113][SAAS:SAAS01036591] Publication Abstract from PubMedNonstructural protein 1 (NS1) is a multifunctional virulence factor of influenza virus. The effector domain (ED) of influenza viruses is capable of binding to a variety of host factors, however, the molecular basis of the interactions remains to be investigated. The isolated NS1-ED exists in equilibrium between the monomer and homodimer. Although the structural diversity of the dimer interface has been well-characterized, limited information is available regarding the internal conformational heterogeneity of the monomeric NS1-ED. Here, we present the solution NMR structure of the NS1-ED W187R of the 1918 influenza A virus, which caused the "Spanish flu." Structural plasticity is an essential property to understand the molecular mechanism by which NS1-ED interacts with multiple host proteins. Structural comparison with the NS1-ED from influenza A/Udorn/1972 (Ud) strain revealed a similar overall structure but a distinct conformational variation and flexibility. Our results suggest that conformational flexibility of the NS1-ED might differ depending on the influenza strain. The structure and conformational plasticity of the nonstructural protein 1 of the 1918 influenza A virus.,Shen Q, Cho JH Biochem Biophys Res Commun. 2019 Oct 8;518(1):178-182. doi:, 10.1016/j.bbrc.2019.08.027. Epub 2019 Aug 14. PMID:31420169[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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