Effect of the N-terminal glycine on the secondary structure, orientation, and interaction of the influenza hemagglutinin fusion peptide with lipid bilayers
Effect of the N-terminal glycine on the secondary structure, orientation, and interaction of the influenza hemagglutinin fusion peptide with lipid bilayers
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DOI：
10.1016/s0006-3495(96)79793-x
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发表时间：
1996-05-01
影响因子：
3.4
通讯作者：
Tamm, LK
中科院分区：
文献类型：
--
作者：
Gray, C;Tatulian, SA;Tamm, LK
流感病毒血凝素（HA）膜锚定亚基的氨基末端片段在膜融合中起关键作用，因此被称为融合肽。我们已经研究了二级结构，方向，并相应于野生型和几个融合和非融合突变体的流感HA融合肽的N-末端改变的双层结构的影响，通过荧光，圆二色性，和傅立叶变换红外光谱，所有的肽含有α-螺旋和β-链构象的片段。在野生型融合肽中，所有残基的40%类似于α-二级结构，30%类似于β-二级结构。相比之下，非融合肽表现出更大的β/α二级结构比。基于各自吸收带的红外二色性，分别测量野生型融合肽的β链的螺旋和酰胺羰基的有序参数。发现野生型肽的两个片段的有序参数在0.1-0.7的范围内，这表明它们最有可能以与膜法线成斜角的方式排列。非融合肽而不是融合肽诱导了在类似于1735 cm（-1）处的红外吸收带的分裂，这被归因于脂质酯羰基键的伸缩振动。其报道了在脂酯羰基与融合肽的水和/或供氢基团之间形成的氢键的改变，与肽的β/α比相关，表明未配对的β链可以取代水分子并与脂酯羰基形成氢键。在融合肽的极端N-末端由单个氨基酸置换诱导的深刻的结构变化进一步表明，当融合肽结合到脂质双层时，三级或四级结构相互作用可能是重要的。
The amino-terminal segment of the membrane-anchored subunit of influenza hemagglutinin (HA) plays a crucial role in membrane fusion and, hence, has been termed the fusion peptide. We have studied the secondary structure, orientation, and effects on the bilayer structure of synthetic peptides corresponding to the wild-type and several fusogenic and nonfusogenic mutants with altered N-termini of the influenza HA fusion peptide by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy, All peptides contained segments of alpha-helical and beta-strand conformation. In the wild-type fusion peptide, similar to 40% of all residues were in alpha-secondary and similar to 30% in beta-secondary structures, By comparison, the nonfusogenic peptides exhibited larger beta/alpha secondary structure ratios. The order parameters of the helices and the amide carbonyl groups of the beta-strands of the wild-type fusion peptide were measured seperately, based on the infrared dichroism of the respective absorption bands. Order parameters in the range 0.1-0.7 were found for both segments of the wild-type peptide, which indicates that they are most likely aligned at oblique angles to the membrane normal, The nonfusogenic but not the fusogenic peptides induced splitting of the infrared absorption band at similar to 1735 cm(-1), which is assigned to stretching vibrations of the lipid ester carbonyl bond, This splitting, which reports on an alteration of the hydrogen bonds formed between the lipid ester carbonyls and water and/or hydrogen-donating groups of the fusion peptides, correlated with the beta/alpha ratio of the peptides, suggesting that unpaired beta-strands may replace water molecules and hydrogen-bond to the lipid ester carbonyl groups. The profound structural changes induced by single amino acid replacements at the extreme N-terminus of the fusion peptide further suggest that tertiary or quaternary structural interactions may be important when fusion peptides bind to lipid bilayers.