Structure of influenza virus N7: the last piece of the neuraminidase "jigsaw" puzzle----中国科学院微生物研究所

科研成果

论文题目:	Structure of influenza virus N7: the last piece of the neuraminidase "jigsaw" puzzle
作者:	Sun Xiaoman, Li Qing, Wu Yan, Wang Mingyang, Liu Yue, Qi Jianxun, Vavricka Christopher J, George F Gao*
联系作者:	George F Gao*
刊物名称:	J Virol
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年份:	2014
影响因子:	4.893
论文下载:	http://jvi.asm.org/content/early/2014/05/28/JVI.00805-14.long
摘要:	There are nine subtypes of influenza A virus neuraminidase (NA) (N1-N9). In addition, influenza B also contains NA and there are two influenza NA-like molecules, N10 and N11, which were recently identified from bats. Crystal structures for all of these proteins have been solved with exception to N7 and there is no published report of N6, though a structure has been deposited. Here, we present the N7 and N6 structures at 2.1 A and 1.8 A, respectively. Structural comparison of all NA subtypes shows that both N7 and N6 highly resemble typical group 2 NA structures with some special characteristics, including an additional cavity adjacent to their active sites formed by novel 340-loop conformations. Comparative analysis also revealed new structural insights into the N-glycosylation, calcium binding and second sialic acid binding site of influenza NA. This comprehensive study is critical for understanding the complexity of the most successful influenza drug target and for the structure-based design of novel influenza inhibitors. IMPORTANCE: Influenza viruses impose a great burden on society, by the human-adapted seasonal types, as well as by variants that occasionally jump from the avian-reservoir to infect humans. The surface glycoprotein neuraminidase (NA) is essential for the propagation of the virus and currently the most successfully drug-targeted molecule. Therefore, the structural and functional analysis of NA is critical for the prevention and control of influenza infections. There are nine subtypes of influenza A virus NA (N1-N9). In addition, influenza B also contains NA and there are two influenza NA-like molecules, N10 and N11, which were recently identified in bats. Crystal structures for all of these proteins have been solved and reported with the exception of N7 and N6. The structural analysis of influenza virus N7 and N6 presented in this study therefore complete the puzzle and add to a comprehensive understanding of influenza virus NA.