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

[tetano]

Proc Natl Acad Sci U S A. 2012 Sep 24. [Epub ahead of print]
Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site.
Zhu X, Yang H, Guo Z, Yu W, Carney PJ, Li Y, Chen LM, Paulson JC, Donis RO, Tong S, Stevens J, Wilson IA.
Source

Departments of Molecular Biology and Chemical Physiology, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037.
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 ? and 2.5 ? resolution and A/little yellow-shouldered bat/Guatemala/060/2010 (GU10-060) at 2.0 ?. 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.

PMID:
23012478
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/23012478

 

[tetano]

Re: 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 Sep 24. [Epub ahead of print]
Structural and functional characterization of neuraminidase-like molecule N10 derived from bat influenza A virus.
Li Q, Sun X, Li Z, Liu Y, Vavricka CJ, Qi J, Gao GF.
Source

School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Abstract

The recent discovery of the unique genome of influenza virus H17N10 in bats raises considerable doubt about the origin and evolution of influenza A viruses. It also identifies a neuraminidase (NA)-like protein, N10, that is highly divergent from the nine other well-established serotypes of influenza A NA (N1-N9). The structural elucidation and functional characterization of influenza NAs have illustrated the complexity of NA structures, thus raising a key question as to whether N10 has a special structure and function. Here the crystal structure of N10, derived from influenza virus A/little yellow-shouldered bat/Guatemala/153/2009 (H17N10), was solved at a resolution of 2.20 ?. Overall, the structure of N10 was found to be similar to that of the other known influenza NA structures. In vitro enzymatic assays demonstrated that N10 lacks canonical NA activity. A detailed structural analysis revealed dramatic alterations of the conserved active site residues that are unfavorable for the binding and cleavage of terminally linked sialic acid receptors. Furthermore, an unusual 150-loop (residues 147-152) was observed to participate in the intermolecular polar interactions between adjacent N10 molecules of the N10 tetramer. Our study of influenza N10 provides insight into the structure and function of the sialidase superfamily and sheds light on the molecular mechanism of bat influenza virus infection.

PMID:
23012237
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/23012237