LIPID-ALAMETHICIN INTERACTIONS INFLUENCE ALAMETHICIN ORIENTATION
LIPID-ALAMETHICIN INTERACTIONS INFLUENCE ALAMETHICIN ORIENTATION
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DOI：
10.1016/s0006-3495(91)82144-0
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发表时间：
1991-11-01
影响因子：
3.4
通讯作者：
WU, Y
中科院分区：
文献类型：
--
作者：
HUANG, HW;WU, Y
尽管大多数研究人员都认为桶板结构是对阿拉甲辛导电状态的良好描述，但对其非导电状态存在相互矛盾的解释；在没有施加电场的情况下，一些人在膜表面发现了阿拉甲辛分子，但另一些人发现它们并入了膜的疏水核心中。通过发现膜中阿拉甲霉素的类似相变行为，这个问题得到了解决。作为脂质/肽比率 L/P 和水化学势 mu 的函数，观察到阿拉甲霉素分子在两种状态之间切换：在一种状态下，大多数肽分子平行于膜表面结合；在另一种状态下，大多数肽分子平行于膜表面结合。在另一种情况下，大多数肽分子垂直插入膜中。通过定向圆二色性方法(OCD；Wu，Y.，H.W.Huang，和G.A.Olah，1990，Biophys.J.57：797-806)使用液晶L(α)相中排列的多层样品来监测阿拉甲辛的状态。如果 L/P 超过临界值，则大部分肽分子位于膜表面。如果L/P低于临界值，则当mu较高时，大部分肽分子会掺入膜中；当mu较低时，大部分又回到膜表面。在典型的电压依赖性传导实验中，在施加电压之前，阿拉甲霉素分子在水相和脂相之间处于分配平衡；在脂质相中，脂质/肽的比例使得大多数阿拉甲霉素分子位于膜表面上。这是阿拉甲辛的非导电状态。 OCD分析表明，当阿拉甲霉素在表面状态和插入状态之间变化时，二级结构基本上没有变化。如果我们假设这些表面肽分子由于偶极子电场相互作用而有可能转入膜核形成通道，则可以解释电压门控机制。我们推测这种相变行为是肽分子之间膜介导的分子间相互作用的表现。
Whereas the barrel-stave configuration is accepted by most investigators as a good description of the conducting state of alamethicin, there are conflicting interpretations on its nonconducting state; in the absence of an applied field, some found alamethicin molecules on the membrane surface, but others found them incorporated in the hydrophobic core of the membrane. This problem is resolved by the discovery of a phase-transitionlike behavior of alamethicin in the membrane. As a function of lipid/peptide ratio L/P and the chemical potential of water mu, alamethicin molecules were observed to switch between two states: in one, the majority of the peptide molecules bind parallel to the membrane surface; in another, the majority of the peptide molecules insert perpendicularly into the membrane. The state of alamethicin was monitored by the method of oriented circular dichroism (OCD; Wu, Y., H. W. Huang, and G. A. Olah, 1990, Biophys. J. 57:797-806) using aligned multilayer samples in the liquid crystalline L(alpha) phase. If L/P exceeds a critical value, most of the peptide molecules are on the membrane surface. If L/P is below the critical value, most of the peptide molecules are incorporated in the membrane when mu is high; when mu is low, most of them are again on the membrane surface. In a typical conduction experiment of voltage dependence, alamethicin molecules are in a partition equilibrium between the aqueous phase and the lipid phase before the application of voltage; in the lipid phase, the lipid/peptide ratio is such that most of alamethicin molecules are on the membrane surface. This is the nonconducting state of alamethicin. The OCD analysis showed that there is essentially no change in the secondary structure when alamethicin changes between the surface state and the inserted state. The voltage-gating mechanism can be explained if we assume that these surface peptide molecules probabilistically turn into the membrane core to form channels due to the dipole-electric field interactions. We speculate that the phase-transitionlike behavior is a manifestation of membrane-mediated intermolecular interactions between peptide molecules.