Structural Basis for dsRNA Recognition by NS1 Protein of Influenza A Virus

Journal Article · Thu Jan 01 04:00:00 EST 2009 · Cell

DOI:https://doi.org/10.1038/cr.2008.288· OSTI ID:980504

Cheng, A; Wong, S; Yuan, Y

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 980504
• Report Number(s): BNL--93422-2010-JA
• Journal Information: Cell, Journal Name: Cell Vol. 19; ISSN 0092-8674; ISSN CELLB5
• Country of Publication: United States
• Language: English

Related Subjects

08 HYDROGEN
36 MATERIALS SCIENCE
45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEFENSE
99 GENERAL AND MISCELLANEOUS
CALORIMETRY
CRYSTAL STRUCTURE
HOST
HUMAN POPULATIONS
HYDROGEN
IN VIVO
INFLUENZA
MONOMERS
NATIONAL DEFENSE
PATHOGENS
PROTEINS
RNA
SHIELDS
SUPPORTS
SURFACES
TITRATION
VIRUSES
national synchrotron light source