Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site

Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18903-8. doi: 10.1073/pnas.1212579109. Epub 2012 Sep 24.


Recently, we reported a unique influenza A virus subtype H17N10 from little yellow-shouldered bats. Its neuraminidase (NA) gene encodes a protein that appears to be highly divergent from all known influenza NAs and was assigned as a new subtype N10. To provide structural and functional insights on the bat H17N10 virus, X-ray structures were determined for N10 NA proteins from influenza A viruses A/little yellow-shouldered bat/Guatemala/164/2009 (GU09-164) in two crystal forms at 1.95 Å and 2.5 Å resolution and A/little yellow-shouldered bat/Guatemala/060/2010 (GU10-060) at 2.0 Å. The overall N10 structures are similar to each other and to other known influenza NA structures, with a single highly conserved calcium binding site in each monomer. However, the region corresponding to the highly conserved active site of influenza A N1-N9 NA subtypes and influenza B NA differs substantially. In particular, most of the amino acid residues required for NA activity are substituted, and the putative active site is much wider because of displacement of the 150-loop and 430-loop. These structural features and the fact that the recombinant N10 protein exhibits no, or extremely low, NA activity suggest that it may have a different function than the NA proteins of other influenza viruses. Accordingly, we propose that the N10 protein be termed an NA-like protein until its function is elucidated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Catalytic Domain
  • Chiroptera / virology*
  • Crystallography, X-Ray
  • Evolution, Molecular
  • Influenza A virus / enzymology*
  • Influenza A virus / genetics
  • Influenza A virus / isolation & purification
  • Neuraminidase / chemistry*
  • Neuraminidase / genetics
  • Protein Structure, Secondary
  • Viral Proteins / chemistry*
  • Viral Proteins / genetics


  • Viral Proteins
  • Neuraminidase

Associated data

  • PDB/4GDI
  • PDB/4GDJ
  • PDB/4GEZ