Studies of the minimum hydrophobicity of alpha-helical peptides required to maintain a stable transmembrane association with phospholipid bilayer membranes.
Studies of the minimum hydrophobicity of alpha-helical peptides required to maintain a stable transmembrane association with phospholipid bilayer membranes.
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研究维持与磷脂双层膜稳定跨膜结合所需的 α 螺旋肽的最小疏水性。
DOI：
10.1021/bi061891b
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发表时间：
2007
期刊：
影响因子：
2.9
通讯作者：
McElhaney,RN
中科院分区：
文献类型：
--
作者：
Lewis,RNAH;Liu,F;Krivanek,R;Rybar,P;Hianik,T;Flach,CR;Mendelsohn,R;Chen,Y;Mant,CT;Hodges,RS;McElhaney,RN
研究了几种设计的α-螺旋跨膜肽（acetyl-K2-Lm-An-K2-amide，m +n= 24）的疏水性和疏水残基的分布对其溶液行为和与磷脂相互作用的影响。我们发现，尽管这些肽在水、膜模拟介质和脂质模型膜中表现出很强的α-螺旋形成倾向，但螺旋的稳定性随着Leu含量的降低而降低。此外，它们与反相高效液相色谱柱的结合在很大程度上取决于它们的疏水性，并且通常随着Leu/Ala比率的降低而降低。然而，这些肽的保留由这样的列也受到疏水残基在其螺旋表面上的分布的影响，进一步增强时，通过聚集疏水残基在螺旋的一侧上的肽螺旋疏水矩增加。疏水残基的这种聚集也增加了肽在水性介质中自聚集的倾向，并增强了肽在脂质双层膜中的分配。我们还发现，肽LA 3LA 2 [乙酰基-K2-（LAAALAA）3LAA-K2-酰胺]，特别是LA 6 [乙酰基-K2-（LAAAAAA）3LAA-K2-酰胺]与磷脂酰胆碱双层的热致相行为的关联不太强烈，并且对磷脂酰胆碱双层的热致相行为的干扰远小于具有较高L/A比的肽。这些结果是一致的自由能计算的这些肽之间的水和磷脂双层，这表明，LA 3LA 2有一个平等的倾向，分配到水和磷脂模型膜的疏水性核心，而LA 6应该强烈倾向于水相的分区。我们的结论是，对于这种类型的α-螺旋肽，Leu/Ala比值大于7/17是与磷脂双层稳定跨膜缔合所必需的。
The effects of the hydrophobicity and the distribution of hydrophobic residues on the surfaces of some designed α-helical transmembrane peptides (acetyl-K2-Lm-An-K2-amide, wherem+n= 24) on their solution behavior and interactions with phospholipids were examined. We find that although these peptides exhibit strong α-helix forming propensities in water, membrane-mimetic media, and lipid model membranes, the stability of the helices decreases as the Leu content decreases. Also, their binding to reversed phase high-performance liquid chromatography columns is largely determined by their hydrophobicity and generally decreases with decreases in the Leu/Ala ratio. However, the retention of these peptides by such columns is also affected by the distribution of hydrophobic residues on their helical surfaces, being further enhanced when peptide helical hydrophobic moments are increased by clustering hydrophobic residues on one side of the helix. This clustering of hydrophobic residues also increases peptide propensity for self-aggregation in aqueous media and enhances partitioning of the peptide into lipid bilayer membranes. We also find that the peptides LA3LA2[acetyl-K2-(LAAALAA)3LAA-K2-amide] and particularly LA6[acetyl-K2-(LAAAAAA)3LAA-K2-amide] associate less strongly with and perturb the thermotropic phase behavior of phosphatidylcholine bilayers much less than peptides with higher L/A ratios. These results are consistent with free energies calculated for the partitioning of these peptides between water and phospholipid bilayers, which suggest that LA3LA2has an equal tendency to partition into water and into the hydrophobic core of phospholipid model membranes, whereas LA6should strongly prefer the aqueous phase. We conclude that for α-helical peptides of this type, Leu/Ala ratios of greater than 7/17 are required for stable transmembrane associations with phospholipid bilayers.