Volume 19, No 2, Feb 2009

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 19 Issue 2, February 2009: 187-195

ORIGINAL ARTICLES

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

Ao Cheng^1,2, Sek Man Wong² and Y Adam Yuan^1,2

¹Genome and Structural Biology Program, Temasek Life Sciences Laboratory, National University of Singapore, 1 Research Link, Singapore 117604, Singapore

²Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, Singapore Correspondence: Y Adam Yuan,(adam@tll.org.sg)

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 1.7Å. 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 α-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

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