A Second RNA-Binding Site in the NS1 Protein of Influenza B Virus

Li Chung Ma, Rongjin Guan, Keith Hamilton, James M. Aramini, Lei Mao, Shanshan Wang, Robert M. Krug, Gaetano T. Montelione

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1562-1572
Number of pages11
JournalStructure
Volume24
Issue number9
DOIs
StatePublished - Sep 6 2016

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Structural Biology

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