Tweet
Proc Natl Acad Sci USA. Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site
[Source: Proceedings of the National Academy of the Sciences of the United States of America, full text: (LINK). Abstract, edited.]
Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site
Xueyong Zhu<SUP>a</SUP>,<SUP>1</SUP>, Hua Yang<SUP>b</SUP>,<SUP>1</SUP>, Zhu Guo<SUP>b</SUP>, Wenli Yu<SUP>a</SUP>, Paul J. Carney<SUP>b</SUP>, Yan Li<SUP>c</SUP>, Li-Mei Chen<SUP>b</SUP>, James C. Paulson<SUP>a</SUP>,<SUP>d</SUP>, Ruben O. Donis<SUP>b</SUP>, Suxiang Tong<SUP>c</SUP>, James Stevens<SUP>b</SUP>,<SUP>2</SUP>, and Ian A. Wilson<SUP>a</SUP>,<SUP>e</SUP>,<SUP>2</SUP>
<SUP></SUP>
Author Affiliations: Departments of <SUP>a</SUP>Molecular Biology and <SUP>d</SUP>Chemical Physiology, <SUP>e</SUP>Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037; and <SUP>b</SUP>Influenza Division and <SUP>c</SUP>Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333
Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved August 30, 2012 (received for review July 23, 2012)
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. Footnotes
- ------
<SUP></SUP>
Author Affiliations: Departments of <SUP>a</SUP>Molecular Biology and <SUP>d</SUP>Chemical Physiology, <SUP>e</SUP>Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037; and <SUP>b</SUP>Influenza Division and <SUP>c</SUP>Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333
Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved August 30, 2012 (received for review July 23, 2012)
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. Footnotes
- <SUP>1</SUP>X.Z. and H.Y. contributed equally to this work.
- <SUP>2</SUP>To whom correspondence may be addressed. E-mail: fwb4@cdc.gov or wilson@scripps.edu.
- Author contributions: X.Z., H.Y., J.S., and I.A.W. designed research; X.Z., H.Y., Z.G., W.Y., and P.J.C. performed research; X.Z., H.Y., Y.L., L.-M.C., R.O.D., S.T., J.S., and I.A.W. contributed new reagents/analytic tools; X.Z., H.Y., J.C.P., R.O.D., S.T., J.S., and I.A.W. analyzed data; and X.Z., H.Y., J.C.P., R.O.D., S.T., J.S., and I.A.W. wrote the paper.
- The authors declare no conflict of interest.
- This article is a PNAS Direct Submission.
- Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID codes 4GDI, 4GDJ, and 4GEZ).
- See Commentary on page 18635.
- This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1212579109/-/DCSupplemental.