Structural basis for dsRNA recognition by NS1 protein of influenza A virus

流行性感冒 A 病毒是引起周期的流行威胁的重要人的病原体。Nonstructural 蛋白质 1 (NS1 ) 流行性感冒的蛋白质一个病毒(NS1A ) 对主人防卫防护病毒。这里，我们报导在 1.7 点绑在双 stranded RNA (dsRNA ) 的 NS1A RNA 有约束力的领域(RBD ) 的水晶结构 ? 。NS1A RBD 形成 homodimer 由它二聚的反平行的伪 - helices 形成的保存凹面表面在一个长度无关的模式认出 A 形式 dsRNA 的主要的沟。dsRNA 被广泛的氢契约被一双不变的精氨酸(Arg38 ) 从两单体抛锚。根据结构的观察，唯一的 Arg38-Arg38 对和二 Arg35-Arg46 配对的等温的滴定热量测定试金表演为 dsRNA 绑定是关键的，并且那 Ser42 和 Thr49 为 dsRNA 绑定也是重要的。Agrobacterium 合作渗入试金进一步支持唯一的 Arg38 对在在 vivo 有约束力的 dsRNA 起重要作用。

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 a-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.