Mechanism of alamethicin insertion into lipid bilayers
Mechanism of alamethicin insertion into lipid bilayers
复制标题
DOI：
10.1016/s0006-3495(96)79458-4
复制
发表时间：
1996-11-01
影响因子：
3.4
通讯作者：
Huang, HW
中科院分区：
文献类型：
--
作者：
He, K;Ludtke, SJ;Huang, HW
丙甲霉素在低肽浓度下吸附在膜表面上。然而，在临界肽与脂质比（P/L）以上，一部分肽分子插入膜中。该临界比率是脂质依赖性的。对于二植烷酰磷脂酰胆碱，约为1/40。在大于或等于1/15的甚至更高的浓度P/L下，所有丙甲霉素插入膜中并形成如通过中子面内散射检测的明确限定的孔。先前的X射线衍射测量表明，吸附在表面上的丙甲霉素具有与肽浓度成比例地使双层变薄的效果。一项理论研究表明，膜变薄的能量消耗确实会导致肽插入。本文将前人的研究推广到P/L > 1/40的高浓度区。X-射线衍射显示，当P/L > 1/23时，当插入接近100%时，双层厚度随肽浓度增加。厚度随插入百分比的变化与双层的烃区域与插入肽的疏水区域相匹配的假设一致。本文讨论了含肽吸附和插入的脂双层弹性能。在简化的一维模型中，吉布斯自由能被计算为P/L和插入phi百分比的函数。该模型表现出插入相变与数据定性一致，我们得出结论，膜变形能是丙甲霉素插入转变的主要驱动力。
Alamethicin adsorbs on the membrane surface at low peptide concentrations. However, above a critical peptide-to-lipid ratio (P/L), a fraction of the peptide molecules insert in the membrane. This critical ratio is lipid dependent. For diphytanoyl phosphatidylcholine it is about 1/40. At even higher concentrations P/L greater than or equal to 1/15, all of the alamethicin inserts into the membrane and forms well-defined pores as detected by neutron in-plane scattering. A previous x-ray diffraction measurement showed that alamethicin adsorbed on the surface has the effect of thinning the bilayer in proportion to the peptide concentration. A theoretical study showed that the energy cost of membrane thinning can indeed lead to peptide insertion. This paper extends the previous studies to the high-concentration region P/L > 1/40. X-ray diffraction shows that the bilayer thickness increases with the peptide concentration for P/L > 1/23 as the insertion approaches 100%. The thickness change with the percentage of insertion is consistent with the assumption that the hydrocarbon region of the bilayer matches the hydrophobic region of the inserted peptide. The elastic energy of a lipid bilayer including both adsorption and insertion of peptide is discussed. The Gibbs free energy is calculated as a function of P/L and the percentage of insertion phi in a simplified one-dimensional model. The model exhibits an insertion phase transition in qualitative agreement with the data, We conclude that the membrane deformation energy is the major driving force for the alamethicin insertion transition.