Perturbation of the hydrophobic core of lipid bilayers by the human antimicrobial peptide LL-37
Perturbation of the hydrophobic core of lipid bilayers by the human antimicrobial peptide LL-37
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DOI：
10.1021/bi036284s
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发表时间：
2004-07-06
期刊：
影响因子：
2.9
通讯作者：
Ramamoorthy, A
中科院分区：
文献类型：
--
作者：
Henzler-Wildman, KA;Martinez, GV;Ramamoorthy, A
LL-37 是一种在人体中发现的阳离子两亲性 a 螺旋抗菌肽，可通过破坏细胞膜来杀死细胞。为了破坏细胞膜，LL-37 等抗菌肽必须改变双层的疏水核心。对酰基链全氘化脂质的差示扫描量热法和氘 (H-2) NMR 实验表明，LL-37 插入双层的疏水区域并改变链堆积和协同性。结果表明，LL-37 与疏水酰基链之间的疏水相互作用对于该肽破坏脂质双层的能力与其与极性头基的静电相互作用同样重要。 H-2 NMR 数据与先前确定的 LL-37 表面取向一致（Henzler Wildman, K. A., et al. (2003) Biochemistry 42, 6545），两亲螺旋的疏水面渗透到双层疏水内部的估计深度为 5-6 埃。 LL-37 还以随脂质类型和温度变化的方式改变脂质双层的材料特性，包括每个脂质的面积、疏水厚度和热膨胀系数。比较不同温度下 LL-37 对 1-棕榈酰-2-油酰-磷脂酰胆碱 (POPC-d(31)) 和 1,2-二肉豆蔻酰-磷脂酰胆碱 (DMPC-d(54)) 的影响，证明了双层顺序在确定 LL-37 对疏水核心的无序和破坏的类型和程度方面的重要性。一种可能的解释是，双层顺序影响 LL-37 插入双层疏水/亲水界面的深度，改变肽和脂质之间静电和疏水相互作用的平衡，该解释解释了此处提供的 H-2 NMR 数据和相同条件下已知的 LL-37 表面取向。
LL-37 is a cationic, amphipathic a-helical antimicrobial peptide found in humans that kills cells by disrupting the cell membrane. To disrupt membranes, antimicrobial peptides such as LL-37 must alter the hydrophobic core of the bilayer. Differential scanning calorimetry and deuterium (H-2) NMR experiments on acyl chain perdeuterated lipids demonstrate that LL-37 inserts into the hydrophobic region of the bilayer and alters the chain packing and cooperativity. The results show that hydrophobic interactions between LL-37 and the hydrophobic acyl chains are as important for the ability of this peptide to disrupt lipid bilayers as its electrostatic interactions with the polar headgroups. The H-2 NMR data are consistent with the previously determined surface orientation of LL-37 (Henzler Wildman, K. A., et al. (2003) Biochemistry 42, 6545) with an estimated 5-6 Angstrom depth of penetration of the hydrophobic face of the amphipathic helix into the hydrophobic interior of the bilayer. LL-37 also alters the material properties of lipid bilayers, including the area per lipid, hydrophobic thickness, and coefficient of thermal expansion in a manner that varies with lipid type and temperature. Comparison of the effect of LL-37 on 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC-d(31)) and 1,2-dimyristoyl-phosphatidylcholine (DMPC-d(54)) at different temperatures demonstrates the importance of bilayer order in determining the type and extent of disordering and disruption of the hydrophobic core by LL-37. One possible explanation, which accounts for both the H-2 NMR data presented here and the known surface orientation of LL-37 under identical conditions, is that bilayer order influences the depth of insertion of LL-37 into the hydrophobic/hydrophilic interface of the bilayer, altering the balance of electrostatic and hydrophobic interactions between the peptide and the lipids.