Mechanism of structural transformations induced by antimicrobial peptides in lipid membranes
Mechanism of structural transformations induced by antimicrobial peptides in lipid membranes
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DOI：
10.1016/j.bbamem.2011.11.002
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发表时间：
2012-02-01
影响因子：
3.4
通讯作者：
Lee, Ka Yee C.
中科院分区：
文献类型：
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作者：
Lam, Kin Lok H.;Wang, Hao;Lee, Ka Yee C.
长期以来，人们一直认为孔的形成是抗菌肽（AMP）增加膜通透性的原因。为了更好地了解 AMP 活性的机制，使用原子力显微镜研究了阳离子抗菌肽 protegrin-1 (PG-1) 对模型膜的破坏。我们在这里展示了两性离子 1,2-二肉豆蔻酰-单甘油-磷酸胆碱 (DMPC) 膜上 PG-1 诱导的支持脂质双层斑块中全方位结构转变的直接可视化。当 PG-1 添加到 DMPC 中时，该肽首先在低浓度下引起边缘不稳定性，然后在中等浓度下引起孔状表面缺陷，最后在高浓度下引起具有特定长度尺度的蠕虫状结构。这些结构的形成可以使用脂质和肽的二元混合物的中间相框架来理解，其中PG-1充当线活性剂。对边缘或内部位置有 PG-1 分子的脂质双层带进行原子分子动力学模拟，以计算 PG-1 降低线张力的效果。使用由 PG-1、DMPC 和水的随机混合物无偏组装含有 PG-1 的双层，进一步研究 PG-1 的位置及其与双层缺陷的关联。这项工作还提出了 AMP 诱导结构转变的通用模型。本文是题为“膜蛋白结构和功能”的特刊的一部分。 (C) 2011 Elsevier B.V. 保留所有权利。
It has long been suggested that pore formation is responsible for the increase in membrane permeability by antimicrobial peptides (AMPs). To better understand the mechanism of AMP activity, the disruption of model membrane by protegrin-1 (PG-1), a cationic antimicrobial peptide, was studied using atomic force microscopy. We present here the direct visualization of the full range of structural transformations in supported lipid bilayer patches induced by PG-1 on zwitterionic 1,2-dimyristoyl-snglycero-phospho-choline (DMPC) membranes. When PG-1 is added to DMPC, the peptide first induces edge instability at low concentrations, then pore-like surface defects at intermediate concentrations, and finally wormlike structures with a specific length scale at high concentrations. The formation of these structures can be understood using a mesophase framework of a binary mixture of lipids and peptides, where PG-1 acts as a line-active agent. Atomistic molecular dynamics simulations on lipid bilayer ribbons with PG-1 molecules placed at the edge or interior positions are carried out to calculate the effect of PG-1 in reducing line tension. Further investigation of the placement of PG-1 and its association with defects in the bilayer is carried out using unbiased assembly of a PG-1 containing bilayer from a random mixture of PG-1, DMPC, and water. A generalized model of AMP induced structural transformations is also presented in this work. This article is part of a Special Issue entitled: Membrane protein structure and function. (C) 2011 Elsevier B.V. All rights reserved.