Influence of Hydrophobic Mismatch on Structures and Dynamics of Gramicidin A and Lipid Bilayers
Influence of Hydrophobic Mismatch on Structures and Dynamics of Gramicidin A and Lipid Bilayers
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DOI：
10.1016/j.bpj.2012.03.014
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发表时间：
2012-04-04
影响因子：
3.4
通讯作者：
Im, Wonpil
中科院分区：
文献类型：
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作者：
Kim, Taehoon;Lee, Kyu Il;Im, Wonpil
短杆菌肽A（gA）是具有交替L-D序列的15个氨基酸的抗生素肽，其在生物膜和合成双层中形成（二聚体）跨双层单价阳离子通道。我们进行了分子动力学模拟的gA二聚体和单体在全原子，明确的二月桂酰磷脂酰胆碱（DLPC），二肉豆蔻酰磷脂酰胆碱（DMPC），二油酰磷脂酰胆碱（DOPC），和1-棕榈酰1 -2-油酰磷脂酰胆碱（POPC）双层。这些不同的磷脂之间的酰基链长度的变化提供了一种方式来改变GA-双层相互作用，通过改变双层疏水厚度，并确定疏水性错配的影响，两个GA通道（和单体亚基）和主机双层的结构和动力学。模拟结果表明，通道结构变化不大的疏水性错配的变化，和脂质双层适应跨双层通道，以尽量减少疏水残基的暴露。双层的厚度，但是，没有单调变化的函数，从通道的径向距离。在所有模拟中，在距沟道4-5埃内存在厚度的初始减小，随后是DOPC和POPC的增加或DLPC和DMPC双层的进一步减小。除了DMPC的三个独立模拟之一和所有三个DLPC模拟，其中双层变薄，以允许一个单一的亚基，以形成一个双层跨越水渗透孔的单体模拟中的双层厚度变化不大。局部脂质面积和双层可压缩性的径向依赖性也是非单调的，在第一壳周围的GA二聚体由于GA-磷脂相互作用和疏水失配。顺序参数，酰基链动力学和扩散常数也不同的脂质在第一壳和散装。在第一壳围绕gA二聚体的脂质行为比从一个简单的错配模型预测的更复杂，这对理解膜蛋白-脂质相互作用的能量学有影响。
Gramicidin A (gA) is a 15-amino-acid antibiotic peptide with an alternating L-D sequence, which forms (dimeric) bilayer-spanning, monovalent cation channels in biological membranes and synthetic bilayers. We performed molecular dynamics simulations of gA dimers and monomers in all-atom, explicit dilauroylphosphatidylcholine (DLPC), dimyristoylphosphatidylcholine (DMPC), dioleoylphosphatidylcholine (DOPC), and 1-palmitoy1-2-oleoyl-phosphatidylcholine (POPC) bilayers. The variation in acyl chain length among these different phospholipids provides a way to alter gA-bilayer interactions by varying the bilayer hydrophobic thickness, and to determine the influence of hydrophobic mismatch on the structure and dynamics of both gA channels (and monomeric subunits) and the host bilayers. The simulations show that the channel structure varied little with changes in hydrophobic mismatch, and that the lipid bilayer adapts to the bilayer-spanning channel to minimize the exposure of hydrophobic residues. The bilayer thickness, however, did not vary monotonically as a function of radial distance from the channel. In all simulations, there was an initial decrease in thickness within 4-5 angstrom from the channel, which was followed by an increase in DOPC and POPC or a further decrease in DLPC and DMPC bilayers. The bilayer thickness varied little in the monomer simulations except one of three independent simulations for DMPC and all three DLPC simulations, where the bilayer thinned to allow a single subunit to form a bilayer-spanning water-permeable pore. The radial dependence of local lipid area and bilayer compressibility is also nonmonotonic in the first shell around gA dimers due to gA-phospholipid interactions and the hydrophobic mismatch. Order parameters, acyl chain dynamics, and diffusion constants also differ between the lipids in the first shell and the bulk. The lipid behaviors in the first shell around gA dimers are more complex than predicted from a simple mismatch model, which has implications for understanding the energetics of membrane protein-lipid interactions.