Gramicidin A Channel Formation Induces Local Lipid Redistribution I: Experiment and Simulation
Gramicidin A Channel Formation Induces Local Lipid Redistribution I: Experiment and Simulation
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DOI：
10.1016/j.bpj.2017.01.028
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发表时间：
2017-03-28
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：
Beaven, Andrew H.;Maer, Andreia M.;Im, Wonpil
完整的膜蛋白功能可以通过宿主双分子层来调节。由于生物膜是多样性和不均匀的，我们探索的后果，脂质多样性使用短杆菌肽A通道嵌入磷脂酰胆碱（PC）双层组成的等摩尔混合物的二油酰-PC和二芥酸-PC（分别为dC（18：1）+dC（22：1））、二棕榈油酰基- PC和二神经酰基-PC（分别为dC（16：1）+dC（24：1））和二-二十烯酰基-PC（纯dC（20：1）），所有这些具有相同的平均双层链长。单通道的寿命实验，分子动力学模拟，和一个简单的脂质压缩模型串联使用，以深入了解周围的通道，这部分地解释了与通道形成的双层变形能量的脂质再分配。相对于单组分dC（20：1）对照双层（65510 ms），双组分双层中的平均单通道寿命（dC（18：1）+dC（22：1）为95 +/- 10 ms，dC（16：1）+dC（24：1）为195 +/- 20 ms）增加，这意味着脂质再分布。使用通道寿命的厚度依赖性变化的理论处理，在dC（18：1）+dC（22：1）和dC（16：1）+dC（24：1）双层中，通道周围脂质的有效局部富集估计分别为5854%dC（18：1）和6652%dC（16：1）。3.5-ms分子动力学模拟显示，在dC（16：1）+dC（24：1）双层中通道周围的第一脂质壳中有66 +/-2%dC 16：1，但没有显著的再分布（50 +/- 4% dC 18：1）;这些模拟值在实验平均值的95%置信区间内。在dC（16：1）+dC（24：1）混合物中对通道附近的更好匹配脂质（dC（16：1））的强烈偏好以及在dC（18：1）+dC（22：1）混合物中的较少再分布可以通过与压缩脂质以匹配通道的疏水长度相关的能量成本来解释。
Integral membrane protein function can be modulated by the host bilayer. Because biological membranes are diverse and nonuniform, we explore the consequences of lipid diversity using gramicidin A channels embedded in phosphatidylcholine (PC) bilayers composed of equimolar mixtures of di-oleoyl-PC and di-erucoyl-PC (dC(18: 1)+dC(22: 1), respectively), di-palmitoleoyl- PC and di-nervonoyl-PC (dC(16: 1)+dC(24: 1), respectively), and di-eicosenoyl-PC (pure dC(20: 1)), all of which have the same average bilayer chain length. Single-channel lifetime experiments, molecular dynamics simulations, and a simple lipid compression model are used in tandem to gain insight into lipid redistribution around the channel, which partially alleviates the bilayer deformation energy associated with channel formation. The average single-channel lifetimes in the two-component bilayers (95 +/- 10 ms for dC(18: 1)+dC(22: 1) and 195 +/- 20 ms for dC(16: 1)+dC(24: 1)) were increased relative to the single-component dC(20: 1) control bilayer (65510 ms), implying lipid redistribution. Using a theoretical treatment of thickness-dependent changes in channel lifetimes, the effective local enrichment of lipids around the channel was estimated to be 5854% dC(18: 1) and 6652% dC(16: 1) in the dC(18: 1)+dC(22: 1) and dC(16: 1)+dC(24: 1) bilayers, respectively. 3.5-ms molecular dynamics simulations show 66 +/- 2% dC16: 1 in the first lipid shell around the channel in the dC(16: 1)+dC(24: 1) bilayer, but no significant redistribution (50 +/- 4% dC18: 1) in the dC(18: 1)+dC(22: 1) bilayer; these simulated values are within the 95% confidence intervals of the experimental averages. The strong preference for the better matching lipid (dC(16: 1)) near the channel in the dC(16: 1)+dC(24: 1) mixture and lesser redistribution in the dC(18: 1)+dC(22: 1) mixture can be explained by the energetic cost associated with compressing the lipids to match the channel's hydrophobic length.