Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity
Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity
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DOI：
10.1074/jbc.m512280200
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发表时间：
2006-03-03
影响因子：
4.8
通讯作者：
Tamm, LK
中科院分区：
文献类型：
--
作者：
Lai, AL;Park, H;Tamm, LK
流感病毒血凝素融合肽对病毒进入细胞至关重要。先前的研究表明，这种肽在膜融合的pH下在脂质模型膜中采用回飞镖形结构。为了研究回旋镖在融合中的作用，我们改变了几个残基，以稳定这种结构中的扭结并测量融合。其中，突变体E11A和W14A表达的血凝素具有半融合活性和无融合活性，而F9A和N12A对融合无影响。突变肽的结合力和自由能模型膜和他们的能力，扰乱脂质双层结构相关的父全长分子的融合活动。通过NMR和定点自旋标记确定的W14 A的结构特征是指向膜外的柔性扭结，与指向膜内的野生型的更有序的回飞棒形成鲜明对比。因此，需要特定的固定角度的回飞棒结构来支持膜融合。
The fusion peptide of influenza hemagglutinin is crucial for cell entry of this virus. Previous studies showed that this peptide adopts a boomerang- shaped structure in lipid model membranes at the pH of membrane fusion. To examine the role of the boomerang in fusion, we changed several residues proposed to stabilize the kink in this structure and measured fusion. Among these, mutants E11A and W14A expressed hemagglutinins with hemifusion and no fusion activities, and F9A and N12A had no effect on fusion, respectively. Binding enthalpies and free energies of mutant peptides to model membranes and their ability to perturb lipid bilayer structures correlated well with the fusion activities of the parent full-length molecules. The structure of W14A determined by NMR and site- directed spin labeling features a flexible kink that points out of the membrane, in sharp contrast to the more ordered boomerang of the wild- type, which points into the membrane. A specific fixed angle boomerang structure is thus required to support membrane fusion.