Abstract:
UNLABELLED:There are nine subtypes of influenza A virus neuraminidase (NA), N1 to N9. In addition, influenza B virus also contains NA, and there are two influenza virus NA-like molecules, N10 and N11, which were recently identified from bats. Crystal structures for all of these proteins have been solved, with the exception of N7, and there is no published report of N6, although a structure has been deposited in the Protein Data Bank. Here, we present the N7 and N6 structures at 2.1 Å and 1.8 Å, 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 virus 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 to N9). In addition, influenza B virus 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 completes the puzzle and adds to a comprehensive understanding of influenza virus NA.
journal_name
J Viroljournal_title
Journal of virologyauthors
Sun X,Li Q,Wu Y,Wang M,Liu Y,Qi J,Vavricka CJ,Gao GFdoi
10.1128/JVI.00805-14subject
Has Abstractpub_date
2014-08-01 00:00:00pages
9197-207issue
16eissn
0022-538Xissn
1098-5514pii
JVI.00805-14journal_volume
88pub_type
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