Analysis of residues near the fusion peptide in the influenza hemagglutinin structure for roles in triggering membrane fusion.
Analysis of residues near the fusion peptide in the influenza hemagglutinin structure for roles in triggering membrane fusion.
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DOI：
10.1016/j.virol.2007.08.035
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发表时间：
2008-01
期刊：
影响因子：
3.7
通讯作者：
S. Thoennes;Zhu-Nan Li;Byeong-Jae Lee;William A. Langley;J. Skehel;R. Russell;D. Steinhauer
中科院分区：
文献类型：
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作者：
S. Thoennes;Zhu-Nan Li;Byeong-Jae Lee;William A. Langley;J. Skehel;R. Russell;D. Steinhauer
流感病毒进入核内体，其中酸化触发膜融合所需的血凝素糖蛋白（HA）的不可逆构象变化。酸诱导的HA结构重排已被很好地记录，并且已经提出了几种模型来将这些与膜融合的过程相关联。然而，缺乏关于特定残基在结构重排和膜融合起始中的作用的细节。在这里，我们报告的HA的A/爱知/2/68病毒（H3亚型）的研究结果，其中在“融合肽”附近的几个电离残基的变化的突变体进行了分析，其对pH值的影响，在构象变化和膜融合发生。获得了多种表型，包括导致HA稳定性在降低的pH值下增加的取代的实例。特别值得注意的是观察到HA 1位置17处的组氨酸至酪氨酸取代导致HA结构变化和膜融合发生的pH值相对于WT降低0.3。结果进行了讨论有关HA结构重排在低pH值和分支特异性差异附近的融合肽启动的可能机制。
Influenza virus entry occurs in endosomes, where acidification triggers irreversible conformational changes of the hemagglutinin glycoprotein (HA) that are required for membrane fusion. The acid-induced HA structural rearrangements have been well documented, and several models have been proposed to relate these to the process of membrane fusion. However, details regarding the role of specific residues in the initiation of structural rearrangements and membrane fusion are lacking. Here we report the results of studies on the HA of A/Aichi/2/68 virus (H3 subtype), in which mutants with changes at several ionizable residues in the vicinity of the “fusion peptide” were analyzed for their effects on the pH at which conformational changes and membrane fusion occur. A variety of phenotypes was obtained, including examples of substitutions that lead to an increase in HA stability at reduced pH. Of particular note was the observation that a histidine to tyrosine substitution at HA1 position 17 resulted in a decrease in pH at which HA structural changes and membrane fusion take place by 0.3 relative to WT. The results are discussed in relation to possible mechanisms by which HA structural rearrangements are initiated at low pH and clade-specific differences near the fusion peptide.