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

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2009,（2）
• 页码范围: 187-195
• 页数: 9页
• 语种: 英文
• DOI: 10.1038/cr.2008.288

摘要

Influenza A viruses are important human pathogens causing periodic pandemic threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NSI A) shields the virus against host defense. Here, we report the crystal structure of NSIA RNA-binding domain (RBD) bound to a double-stranded RNA (dsRNA) at 1.7A. NSIA 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.