Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage

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	Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage
	Lu, Xishan 1,2; Shi, Yi 2; Gao, Feng 3; Xiao, Haixia 4; Wang, Ming 1; Qi, Jianxun 2; Gao, George F.1,2,4,5
刊名	JOURNAL OF VIROLOGY
	2012-12-01
卷号	86 期号:23 页码:12861-12870
英文摘要	With a new serotype (H17) of hemagglutinin (HA) recently being discovered, there are now 17 serotypes (H1 to H17) of influenza A viruses in total. It is believed that HA is initially expressed as a precursor of HA0 and then cleaved into HA1 and HA2, forming a disulfide bond-linked complex, for its full function. Structural data show that a loop structure exists in the cleavage site between HA1 and HA2, and this flexible loop is crucial for the efficient cleavage of HA0. Here, the crystal structures of H16 (a low-pathogenicity avian influenza virus) in their HA0 form (H16HA0) have been solved at 1.7-angstrom and 2.0-angstrom resolutions. To our surprise, an alpha-helix element in the cleavage site which inserts into the negatively charged cavity with the key residue R329 hidden behind the helix was observed. In vitro trypsin cleavage experiments demonstrated inefficient cleavage of H16HA0 under both neutral and low-pH conditions. The results provide new insights into influenza A virus pathogenicity; both the relatively stable alpha-helix structure in the flexible cleavage loop and inaccessibility of the cleavage site likely contribute to the low pathogenicity of avian influenza A virus. Furthermore, compared to all of the HAs whose structures have been solved, H16 is a good reference for assigning the HA subtypes into two groups on the basis of the three-dimensional structure, which is consistent with the phylogenetic grouping. We conclude that in light of the current H16HA0 structure, the natural alpha-helix element might provide a new opportunity for influenza virus inhibitor design.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Virology
研究领域[WOS]	Virology
关键词[WOS]	A VIRUS ; MEMBRANE-FUSION ; SWINE-ORIGIN ; MAXIMUM-LIKELIHOOD ; RECEPTOR-BINDING ; NEURAMINIDASE ; PROTEIN ; GLYCOPROTEIN ; (H1N1)-2009 ; REFINEMENT
收录类别	SCI
语种	英语
WOS记录号	WOS:000310585300036
内容类型	期刊论文
源URL	[http://124.16.173.210/handle/834782/1312]
专题	天津工业生物技术研究所_蛋白质工程与疫苗实验室高福_期刊论文
作者单位	1.China Agr Univ, Coll Vet Med, Beijing 100094, Peoples R China 2.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China 3.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100080, Peoples R China 4.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Lab Prot Engn & Vaccines, Tianjin, Peoples R China 5.Chinese Acad Sci, Beijing Inst Life Sci, Res Network Immun & Hlth RNIH, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Lu, Xishan,Shi, Yi,Gao, Feng,et al. Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage[J]. JOURNAL OF VIROLOGY,2012,86(23):12861-12870.
APA	Lu, Xishan.,Shi, Yi.,Gao, Feng.,Xiao, Haixia.,Wang, Ming.,...&Gao, George F..(2012).Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage.JOURNAL OF VIROLOGY,86(23),12861-12870.
MLA	Lu, Xishan,et al."Insights into Avian Influenza Virus Pathogenicity: the Hemagglutinin Precursor HA0 of Subtype H16 Has an Alpha-Helix Structure in Its Cleavage Site with Inefficient HA1/HA2 Cleavage".JOURNAL OF VIROLOGY 86.23(2012):12861-12870.