title: Structural Basis for a Novel Interaction between the NS1 Protein Derived from the 1918 Influenza Virus and RIG-I.
abstract: The influenza non-structural protein 1 (NS1) plays a critical role in antagonizing the innate immune response to infection. One interaction that facilitates this function is between NS1 and RIG-I, one of the main sensors of influenza virus infection. While NS1 and RIG-I are known to interact, it is currently unclear whether this interaction is direct or if it is mediated by other biomolecules. Here we demonstrate a direct, strain-dependent interaction between the NS1 RNA binding domain (NS1(RBD)) of the influenza A/Brevig Mission/1918 H1N1 (1918(H1N1)) virus and the second caspase activation and recruitment domain of RIG-I. Solving the solution structure of the 1918(H1N1) NS1(RBD) revealed features in a functionally novel region that may facilitate the observed interaction. The biophysical and structural data herein suggest a possible mechanism by which strain-specific differences in NS1 modulate influenza virulence.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Jureka
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Alex B
authors.initials: AB
authors.lastname: Kleinpeter
authors.affiliation: National Magnetic Resonance Facility at Madison, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cornilescu
authors.affiliation: National Magnetic Resonance Facility at Madison, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Cornilescu
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: cpetit@uab.edu.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Petit
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry; D064149:Influenza Pandemic, 1918-1919; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011971:Receptors, Immunologic; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C085820:INS1 protein, influenza virus; D011971:Receptors, Immunologic; D017361:Viral Nonstructural Proteins; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases