title: Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site.
abstract: 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.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Xueyong
authors.initials: X
authors.lastname: Zhu
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Guo
authors.forename: Wenli
authors.initials: W
authors.lastname: Yu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Carney
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Chen
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
authors.forename: Ruben O
authors.initials: RO
authors.lastname: Donis
authors.forename: Suxiang
authors.initials: S
authors.lastname: Tong
authors.forename: James
authors.initials: J
authors.lastname: Stevens
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002685:Chiroptera / Q000821:virology*; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D009980:Influenza A virus / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D009439:Neuraminidase / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D014764:Viral Proteins; D009439:Neuraminidase