The Analysis of the Structure of Receptor Binding Site of Hemagglutin in Molecule of Influenza A Virus and of the Characteristics of Receptor.

甲型流感病毒分子血凝素受体结合位点结构分析及受体特性。

• 批准号: 63480157
• 负责人: NAKAJIMA Katsuhisa
• 金额: $ 4.29万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480157/
• 关键词: Influenza a Virus; Amino Acid Sequence of Ha; Receptor Binding Site; Receptor Specificity; 部位突然変異; インフルエンザウイルス; 血球凝集素; レセプタ-結合領域; シグナルペプチド; シアル酸結合部位

We have studied the receptor binding structure on the hemagglutinin (HA) protein of the influenza A virus using two different methods.First, we synthesized cDNAs of the HA genes of influenza A virus which belong to seven different subtypes and whose nucleotide sequences were not reported until 1989. We compared the amino acid sequences which are composing the putative receptor binding structure among 13 serotype HA proteins and discussed the structural feature of the receptor binding site (ref 10).Secondly, we constructed several mutant HA cDNAs by site-directed mutagenesis and expressed them in mamalian cells. We found that the amino acid residue 226 on the HA protein of the H1 subtype was important for the receptor binding (ref 3, 10).We also investigated the amino acid changes on the HA proteins of the H1 and H3 subtypes of human influenza A virus during the evolution of each subtype and discussed the influence of these amino acid changes to the receptor binding site (ref 2, 4, 9).We have investigated the receptor specificity of HA proteins among 13 different subtypes. We found all HA proteins except H3 subtype have glutamin at the amino acid residue 226, but they bind to Neu2-6Gal or Neu2-3 Gal (ref. 10)

我们用两种不同的方法研究了甲型流感病毒血凝素（HA）蛋白的受体结合结构：首先，我们合成了7种不同亚型的甲型流感病毒HA基因的cDNA，其核苷酸序列直到1989年才被报道。我们比较了13种血清型HA蛋白中与受体结合的氨基酸序列，并讨论了其受体结合位点的结构特征（参考文献10）。其次，我们利用定点突变技术构建了几种突变型HA cDNA，并在哺乳动物细胞中进行了表达。我们发现H1亚型HA蛋白上的氨基酸残基226对于受体结合是重要的我们还研究了H1和H3亚型人A型流感病毒HA蛋白在各亚型进化过程中的氨基酸变化，并讨论了这些氨基酸变化对受体结合位点的影响（参考文献2，4，9）。我们研究了13种不同亚型之间HA蛋白的受体特异性。我们发现除H3亚型外的所有HA蛋白在氨基酸残基226处具有维生素B1，但它们结合Neu 2 - 6 Gal或Neu 2 - 3Gal（参考文献10）。

项目成果

S.Nakajima et al.,: "Localization on the evolutionary tree of influenza H3 hAemagglutinin gene of jApanese strains isolated during 1985ー6 seasons" Epide.Infect.100. 301-310 (1988)

S.Nakajima 等人，“1985-6 季节期间分离的日本菌株的流感 H3 hAemagglutinin 基因进化树上的定位”Epide.Infect.100 (1988)。

M. Kurokawa et al.: "Inhibitory effect of proteinkinase C inhibitor on the replication of influenza type A virus." J. gen. Virol.71.(1990)

M. Kurokawa 等人：“蛋白激酶 C 抑制剂对 A 型流感病毒复制的抑制作用。”

S. NAKAJIMA etal.: "Localization on the evolutionary tree of influenza H3 haemagglutinin genes of Japanese strains isolated during 1985-6 seasons" Epidem. Infect. 100. 301-310. (1988)

S. NAKAJIMA 等人：“1985-6 季节期间分离的日本毒株的流感 H3 血凝素基因进化树上的定位”Epidem。

A. Yamada et al.,: "Epitope changes on the hamagglutinin molecule of recent H1N1 influenza viruses." J. Gen. Virol.

A. Yamada 等人：“最近 H1N1 流感病毒的血凝素分子上的表位发生了变化。”

E.Nobusawa et al.,: "Comparison of amino acid sequences among 13 serotypes of hemagglutinin of influenza A viruses and receptor binding properties." Virology.

E.Nobusawa 等人：“甲型流感病毒血凝素 13 种血清型之间的氨基酸序列比较和受体结合特性。”