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Gaetano T. Montelione Laboratory
CABM Protein NMR Laboratory

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Non-Structural Protein 1

Non-structural protein 1, which is encoded by the influenza A virus, is an RNA-binding protein that is required for virus replication. NS1 has three different RNA-binding activities. First, it binds to the poly A tails of cellular (not viral) pre-mRNAs. NS1 thus retains these pre-mRNAs within the cell's nucleus by blocking their export into the cytoplasm. Second, NS1 blocks pre-mRNA splicing by binding to a stem-buldge in U6 small nuclear RNA (snRNA) thus inactivating any U6-U2 or U6-U4 interactions from taking place that are required for splicing. Lastly, NS1 can bind double-stranded RNA (dsRNA) with a relatively low sequence specificity while maintaining a high affinity which blocks the activation of PKR kinase.
NS1 is a symmetrical dimeric protein consisting of six helical folds. Its novel three-dimensional structure is unlike any other currently in the databases. Each monomeric chain is 73 amino acid residues long, and the polypeptide weighs 18 kDa.
NS1 possessess a positive electrostatic field due to a large amount of basic amino acid residues. Basic residues on the protein's surface may provide important clues to possible nucleic acid binding sites since these residues are highly associated with the binding of both double-stranded and single-stranded nucleic acids.


This picture of NS1 is colored by secondary structure. Corresponding helices are colored the same to show the symmetry of the protein. Helix 1 and 1'=red, Helix 2 and 2'=yellow, and Helix 3 and 3'=green.


This picture depicts the hypothetical model of the complex formed between NS1 and a 16 base pair long stretch of double-stranded RNA (dsRNA).


  • Keywords: Nonstructural protein, RNA-Binding, ssRNA-Binding, dsDNA-Binding, PolyA-RNA-Binding, Dimeric Six Helical Structure
  • View this protein's PDB entry as 1NS1

References

C.Y. Chien, R. Tejero, Y. Huang, D.E. Zimmerman, C.B. Rios, R.M. Krug, G.T. Montelione
A Novel RNA-Binding Motif in Influenza A Virus Non-Structural Protein 1
Nat. Struct. Biol. 4:891 (1997)
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X.Y. Qian, C.Y. Chien, Y. Lu, G.T. Montelione, R.M. Krug
An Amino-Terminal Polypeptide Fragment of the Influenza Virus NS1 Protein Possesses Specific RNA-Binding Activity and Largely Helical Backbone Structure
RNA 1:948 (1995)
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