La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
Sci Rep. 2019 Jul 25;9(1):10841. doi: 10.1038/s41598-019-47325-y.
Melittin is one of the most studied α-helical cationic membrane disrupting peptides. It is the main component of bee venom, however it is considered an antimicrobial peptide for its ability to kill bacteria. Melittin is believed to act by opening large toroidal pores in the plasma membrane of the targeted cells/bacteria, although this is questioned by some authors. Little is known, however, about the molecular mechanism leading to this activity. In this study the mechanism of action of melittin was studied by dye leakage and quartz crystal microbalance fingerprinting analysis in biomimetic model membranes. The results revealed the existence of multiple stages in the membrane disrupting action with characteristic differences between different membrane types. In bacterial-mimetic (charged) lipid mixtures the viscoelastic fingerprints suggest a surface-acting mechanism, whereas in mammalian-mimetic (neutral) membranes melittin appears to penetrate the bilayer already at low concentrations. In domain-forming mixed membranes melittin shows a preference for the domain containing predominantly zwitterionic lipids. The results confirm membrane poration but are inconsistent with the insertion-to-toroidal pore pathway. Therefore hypotheses of the two membrane disrupting pathways were developed, describing the membrane disruption as either surface tension modulation leading to toroidal pore formation, or linear aggregation leading to fissure formation in the membrane.
蜂毒素是研究最多的α-螺旋阳离子膜破坏肽之一。它是蜜蜂毒液的主要成分，但由于其能够杀死细菌，因此被认为是一种抗菌肽。蜂毒素被认为通过在靶细胞/细菌的质膜上打开大的环形孔来发挥作用，尽管一些作者对此提出了质疑。然而，对于导致这种活性的分子机制知之甚少。在这项研究中，通过仿生模型膜中的染料渗漏和石英晶体微天平指纹分析研究了蜂毒素的作用机制。结果表明，在破坏膜的作用中存在多个阶段，不同膜类型之间存在特征差异。在细菌模拟（带电）脂质混合物中，粘弹性指纹表明存在表面作用机制，而在哺乳动物模拟（中性）膜中，蜂毒素似乎在低浓度下就已经穿透双层。在形成域的混合膜中，蜂毒素优先与主要含有两性离子脂质的域结合。结果证实了膜穿孔，但与插入到环形孔途径不一致。因此，提出了两种膜破坏途径的假设，将膜破坏描述为表面张力调制导致环形孔形成，或线性聚集导致膜中裂隙形成。
