Sigmoidal concentration dependence of antimicrobial peptide activities: A case study on alamethicin
Sigmoidal concentration dependence of antimicrobial peptide activities: A case study on alamethicin
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DOI：
10.1016/s0006-3495(02)75452-0
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发表时间：
2002-02-01
影响因子：
3.4
通讯作者：
Huang, HW
中科院分区：
文献类型：
--
作者：
Chen, FY;Lee, MT;Huang, HW
在三种不同的膜条件下，作为肽浓度的函数测量丙甲霉素从其非活性状态到其孔形成活性状态的状态的转变。在每种情况下，占据活性状态的丙甲霉素分子的分数，phi，显示出S形浓度依赖性，这是典型的抗菌肽的活性。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，一个简单的聚合效应不能解释的数据。我们将介绍一个模型的基础上的弹性膜，考虑到膜变薄的影响，由于蛋白质的夹杂物。膜的弹性能为聚集提供了额外的驱动力。该模型产生的关系，不仅预测正确的浓度依赖性，但也定性地解释了依赖性如何随膜条件的变化。结果表明，膜介导的单体和聚集体之间的相互作用是必不可少的强协同性显示在孔形成。
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.