Chen Fang-Yu, Lee Ming-Tao, Huang Huey W
Department of Physics, National Central University, Chung-Li, Taiwan 32054.
Biophys J. 2002 Feb;82(2):908-14. doi: 10.1016/S0006-3495(02)75452-0.
The transition of the state of alamethicin from its inactive state to its active state of pore formation was measured as a function of the peptide concentration in three different membrane conditions. In each case the fraction of the alamethicin molecules occupying the active state, phi, showed a sigmoidal concentration dependence that is typical of the activities of antimicrobial peptides. Such a concentration dependence is often interpreted as due to peptide aggregation. However, we will show that a simple effect of aggregation cannot explain the data. We will introduce a model based on the elasticity of membrane, taking into consideration the membrane-thinning effect due to protein inclusion. The elastic energy of membrane provides an additional driving force for aggregation. The model produces a relation that not only predicts the correct concentration dependence but also explains qualitatively how the dependence changes with membrane conditions. The result shows that the membrane-mediated interactions between monomers and aggregates are essential for the strong cooperativity shown in pore formation.
在三种不同的膜条件下，测量了丙甲菌素从无活性状态转变为形成孔的活性状态的过程，该过程是肽浓度的函数。在每种情况下，处于活性状态的丙甲菌素分子分数φ呈现出S形浓度依赖性，这是抗菌肽活性的典型特征。这种浓度依赖性通常被解释为由于肽聚集。然而，我们将表明，简单的聚集效应无法解释这些数据。我们将引入一个基于膜弹性的模型，考虑到由于蛋白质嵌入导致的膜变薄效应。膜的弹性能为聚集提供额外的驱动力。该模型产生的关系不仅预测了正确的浓度依赖性，还定性地解释了这种依赖性如何随膜条件变化。结果表明，单体与聚集体之间的膜介导相互作用对于孔形成中表现出的强协同性至关重要。
