title: Structural basis for dsRNA recognition by NS1 protein of influenza A virus.
abstract: Influenza A viruses are important human pathogens causing periodic pandemic threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NS1A) shields the virus against host defense. Here, we report the crystal structure of NS1A RNA-binding domain (RBD) bound to a double-stranded RNA (dsRNA) at 1.7A. NS1A RBD forms a homodimer to recognize the major groove of A-form dsRNA in a length-independent mode by its conserved concave surface formed by dimeric anti-parallel alpha-helices. dsRNA is anchored by a pair of invariable arginines (Arg38) from both monomers by extensive hydrogen bonds. In accordance with the structural observation, isothermal titration calorimetry assay shows that the unique Arg38-Arg38 pair and two Arg35-Arg46 pairs are crucial for dsRNA binding, and that Ser42 and Thr49 are also important for dsRNA binding. Agrobacterium co-infiltration assay further supports that the unique Arg38 pair plays important roles in dsRNA binding in vivo.Cell Research (2009) 19:187-195. doi: 10.1038/cr.2008.288; published online 23 September 2008.
authors.affiliation: Genome and Structural Biology Program, Temasek Life Sciences Laboratory, National University of Singapore, 1 Research Link, Singapore 117604, Singapore.
authors.forename: Ao
authors.initials: A
authors.lastname: Cheng
authors.forename: Sek Man
authors.initials: SM
authors.lastname: Wong
authors.forename: Y Adam
authors.initials: YA
authors.lastname: Yuan
mesh_terms: D018360:Crystallography, X-Ray; D019281:Dimerization; D006860:Hydrogen Bonding; D009980:Influenza A virus / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000737:chemistry* / Q000378:metabolism; D034741:RNA, Small Interfering; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C085820:INS1 protein, influenza virus; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D017361:Viral Nonstructural Proteins