Intermediates in influenza induced membrane fusion.
Intermediates in influenza induced membrane fusion.
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DOI：
10.1002/j.1460-2075.1990.tb07871.x
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发表时间：
1990-12
期刊：
影响因子：
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通讯作者：
T. Stegmann;J. M. Whitel;A. Helenius
中科院分区：
文献类型：
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作者：
T. Stegmann;J. M. Whitel;A. Helenius
我们的研究结果表明，流感病毒与靶膜融合的机制涉及血凝素（HA，病毒融合蛋白）和病毒与靶膜之间的接触位点的顺序复杂的变化。为了使各个步骤适合研究，我们在0 ℃下工作，这降低了融合速率并提高了效率。0 ℃和37 ℃下的融合机制相似。该过程开始于HA的构象变化，其暴露融合肽，但不导致三聚体的胞外域的顶部解离。蛋白质的变化导致病毒立即疏水附着到靶脂质体上。附着之后是滞后期（0 ℃下4-8分钟，37 ℃下0.6-2秒），在此期间病毒和脂质体之间的膜接触部位发生重排。经过进一步的一系列变化，最终的双层合并发生了。该最终融合事件不是pH依赖性的。在0 ℃下，发生有效的融合而没有HA三聚体的顶部结构域的解离，表明HA的瞬时构象负责在生理温度下的融合。观察导致HA介导的融合的修正模型。
Our results show that the mechanism by which influenza virus fuses with target membranes involves sequential complex changes in the hemagglutinin (HA, the viral fusion protein) and in the contact site between virus and target membrane. To render individual steps amenable to study, we worked at 0 degree C which decreased the rate of fusion and increased the efficiency. The mechanism of fusion at 0 degree C and 37 degrees C was similar. The process began with a conformational change in HA which exposed the fusion peptides but did not lead to dissociation of the tops of the ectodomain of the trimer. The change in the protein led to immediate hydrophobic attachment of the virus to the target liposomes. Attachment was followed by a lag period (4–8 min at 0 degree C, 0.6–2 s at 37 degrees C) during which rearrangements occurred in the site of membrane contact between the virus and liposome. After a further series of changes the final bilayer merger took place. This final fusion event was not pH dependent. At 0 degree C efficient fusion occurred without dissociation of the top domains of the HA trimer, suggesting that a transient conformation of HA is responsible for fusion at physiological temperatures. The observations lead to a revised model for HA mediated fusion.