Binding of cationic pentapeptides with modified side chain lengths to negatively charged lipid membranes: Complex interplay of electrostatic and hydrophobic interactions
Binding of cationic pentapeptides with modified side chain lengths to negatively charged lipid membranes: Complex interplay of electrostatic and hydrophobic interactions
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DOI：
10.1016/j.bbamem.2012.03.001
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发表时间：
2012-07-01
影响因子：
3.4
通讯作者：
Blume, Alfred
中科院分区：
文献类型：
--
作者：
Hoernke, Maria;Schwieger, Christian;Blume, Alfred
碱性氨基酸在膜相关蛋白与带负电荷的膜的结合中起关键作用。然而，碱性氨基酸如赖氨酸的侧链不仅提供正电荷，而且提供能够实现疏水相互作用的柔性烃间隔物。我们通过改变具有铵基的五肽的侧链长度，从赖氨酸开始到具有较短侧链的赖氨酸类似物，即鸟氨酸（Urn）、α，γ-二氨基丁酸（Dab）和α，β-二氨基丙酸（Dap），研究了疏水性贡献对结合的影响。用量热法、红外光谱法和单层膜技术研究了该聚合物与带负电荷的磷脂酰甘油（PG）膜的结合。这种约束力受到抵消性贡献（有时是补偿性贡献）的影响。结合肽对脂质相行为的影响取决于肽侧链的长度。等温滴定量热法（ITC）的实验表明，作为侧链长度的函数，在不同程度上补偿放热和吸热效应。对于具有较短侧链的肽，脂质相变温度的增加更显著。FTIR光谱显示肽结合后的脂质双层界面的水合作用的变化。使用单分子层技术，可以清楚地观察到静电和疏水效应的贡献。具有短侧链的肽诱导PG单层的表面压力显著降低，而具有额外的疏水相互作用的肽降低的表面压力少得多，甚至导致增加，这表明侧链的疏水部分插入到脂质单层中。(C)2012 Elsevier B. V.保留所有权利。
Basic amino acids play a key role in the binding of membrane associated proteins to negatively charged membranes. However, side chains of basic amino acids like lysine do not only provide a positive charge, but also a flexible hydrocarbon spacer that enables hydrophobic interactions. We studied the influence of hydrophobic contributions to the binding by varying the side chain length of pentapeptides with ammonium groups starting with lysine to lysine analogs with shorter side chains, namely ornithine (Urn), alpha,gamma-diaminobutyric acid (Dab) and alpha, beta-diaminopropionic acid (Dap). The binding to negatively charged phosphatidylglycerol (PG) membranes was investigated by calorimetry, FT-infrared spectroscopy (FT-IR) and monolayer techniques. The binding was influenced by counteracting and sometimes compensating contributions. The influence of the bound peptides on the lipid phase behavior depends on the length of the peptide side chains. Isothermal titration calorimetry (ITC) experiments showed exothermic and endothermic effects compensating to a different extent as a function of side chain length. The increase in lipid phase transition temperature was more significant for peptides with shorter side chains. FTIR-spectroscopy revealed changes in hydration of the lipid bilayer interface after peptide binding. Using monolayer techniques, the contributions of electrostatic and hydrophobic effects could clearly be observed. Peptides with short side chains induced a pronounced decrease in surface pressure of PG monolayers whereas peptides with additional hydrophobic interactions decreased the surface pressure much less or even lead to an increase, indicating insertion of the hydrophobic part of the side chain into the lipid monolayer. (C) 2012 Elsevier B.V. All rights reserved.