Structural basis for dsRNA recognition by NS1 protein of influenza A virus
Structural basis for dsRNA recognition by NS1 protein of influenza A virus
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DOI：
10.1038/cr.2008.288
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发表时间：
2009-02-01
期刊：
影响因子：
44.1
通讯作者：
Yuan, Y. Adam
中科院分区：
文献类型：
--
作者：
Cheng, Ao;Wong, Sek Man;Yuan, Y. Adam
甲型流感病毒是引起周期性大流行威胁的重要人类病原体。A型流感病毒（NS 1A）的非结构蛋白1（NS 1）蛋白保护病毒抵抗宿主防御。在这里，我们报告的晶体结构的NS 1A RNA结合域（RBD）结合到一个双链RNA（dsRNA）在1.7埃。NS 1A RBD形成同源二聚体，通过其由二聚体反平行α-螺旋形成的保守凹面以长度非依赖性模式识别A型dsRNA的大沟。dsRNA由来自两个单体的一对不变的精氨酸（Arg 38）通过广泛的氢键锚定。等温滴定量热分析结果表明，在dsRNA的结合过程中，Arg 38-Arg 38对和Arg 35-Arg 46对是关键的，而Ser 42和Thr 49对dsRNA的结合也很重要。农杆菌共浸润试验进一步支持了独特的Arg 38对在体内dsRNA结合中起重要作用。
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 1.7 angstrom. 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.