Structural Basis for dsRNA Recognition by NS1 Protein of Influenza A Virus
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 Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 980504
- Report Number(s):
- BNL-93422-2010-JA; CELLB5; TRN: US201015%%1889
- Journal Information:
- Cell, Vol. 19; ISSN 0092-8674
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
36 MATERIALS SCIENCE
45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEFENSE
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
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