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

被引:97
作者
Zhu, Xueyong [3 ]
Yang, Hua [1 ]
Guo, Zhu [1 ]
Yu, Wenli [3 ]
Carney, Paul J. [1 ]
Li, Yan [2 ]
Chen, Li-Mei [1 ]
Paulson, James C. [3 ,4 ]
Donis, Ruben O. [1 ]
Tong, Suxiang [2 ]
Stevens, James [1 ]
Wilson, Ian A. [3 ,5 ]
机构
[1] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA 30333 USA
[2] Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA 30333 USA
[3] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[4] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
[5] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
基金
美国国家卫生研究院;
关键词
enzyme; mechanism; receptor; glycoprotein; infection; 3-DIMENSIONAL STRUCTURE; SIALIC-ACID; RESOLUTION; INHIBITOR; CALCIUM; COMPLEX; BINDING;
D O I
10.1073/pnas.1212579109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 angstrom and 2.5 angstrom resolution and A/little yellow-shouldered bat/Guatemala/060/2010 (GU10-060) at 2.0 angstrom. 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.
引用
收藏
页码:18903 / 18908
页数:6
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