TY - JOUR
T1 - A Second RNA-Binding Site in the NS1 Protein of Influenza B Virus
AU - Ma, Li Chung
AU - Guan, Rongjin
AU - Hamilton, Keith
AU - Aramini, James M.
AU - Mao, Lei
AU - Wang, Shanshan
AU - Krug, Robert M.
AU - Montelione, Gaetano T.
N1 - Funding Information:
We thank Drs. L. Cole and J.W. Lary of the University of Connecticut Analytical Ultracentrifugation Facility for providing analytical ultracentrifugation analysis and Dr. R. Xiao for providing AGF-MALS data. We also thank Drs. T.B. Acton, G.V.T. Swapna, and R. Xiao for helpful discussions and comments on this manuscript. This work was supported by National Institute of Allergy and Infectious Disease grants R01-AI11772 (R.M.K.) and R21-AI117510 (G.T.M.), and the National Institute of General Medical Science grant U54 GM094597-05 (G.T.M). G.T.M. is a founder of Nexomics Biosciences.
PY - 2016/9/6
Y1 - 2016/9/6
N2 - Influenza viruses cause a highly contagious respiratory disease in humans. The NS1 proteins of influenza A and B viruses (NS1A and NS1B proteins, respectively) are composed of two domains, a dimeric N-terminal domain and a C-terminal domain, connected by a flexible polypeptide linker. Here we report the 2.0-Å X-ray crystal structure and nuclear magnetic resonance studies of the NS1B C-terminal domain, which reveal a novel and unexpected basic RNA-binding site that is not present in the NS1A protein. We demonstrate that single-site alanine replacements of basic residues in this site lead to reduced RNA-binding activity, and that recombinant influenza B viruses expressing these mutant NS1B proteins are severely attenuated in replication. This novel RNA-binding site of NS1B is required for optimal influenza B virus replication. Most importantly, this study reveals an unexpected RNA-binding function in the C-terminal domain of NS1B, a novel function that distinguishes influenza B viruses from influenza A viruses.
AB - Influenza viruses cause a highly contagious respiratory disease in humans. The NS1 proteins of influenza A and B viruses (NS1A and NS1B proteins, respectively) are composed of two domains, a dimeric N-terminal domain and a C-terminal domain, connected by a flexible polypeptide linker. Here we report the 2.0-Å X-ray crystal structure and nuclear magnetic resonance studies of the NS1B C-terminal domain, which reveal a novel and unexpected basic RNA-binding site that is not present in the NS1A protein. We demonstrate that single-site alanine replacements of basic residues in this site lead to reduced RNA-binding activity, and that recombinant influenza B viruses expressing these mutant NS1B proteins are severely attenuated in replication. This novel RNA-binding site of NS1B is required for optimal influenza B virus replication. Most importantly, this study reveals an unexpected RNA-binding function in the C-terminal domain of NS1B, a novel function that distinguishes influenza B viruses from influenza A viruses.
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U2 - 10.1016/j.str.2016.07.001
DO - 10.1016/j.str.2016.07.001
M3 - Article
C2 - 27545620
AN - SCOPUS:84985945896
VL - 24
SP - 1562
EP - 1572
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 9
ER -