Institute of Physics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 5, 121 16 Prague 2, Czech Republic.
Institute of Organic Chemistry and Biochemistry, v.v.i., Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.
Int J Mol Sci. 2019 Feb 1;20(3):631. doi: 10.3390/ijms20030631.
We have investigated structural changes of peptides related to antimicrobial peptide Halictine-1 (HAL-1) induced by interaction with various membrane-mimicking models with the aim to identify a mechanism of the peptide mode of action and to find a correlation between changes of primary/secondary structure and biological activity. Modifications in the HAL-1 amino acid sequence at particular positions, causing an increase of amphipathicity (Arg/Lys exchange), restricted mobility (insertion of Pro) and consequent changes in antimicrobial and hemolytic activity, led to different behavior towards model membranes. Secondary structure changes induced by peptide-membrane interaction were studied by circular dichroism, infrared spectroscopy, and fluorescence spectroscopy. The experimental results were complemented by molecular dynamics calculations. An α-helical structure has been found to be necessary but not completely sufficient for the HAL-1 peptides antimicrobial action. The role of alternative conformations (such as β-sheet, PPII or 3-helix) also seems to be important. A mechanism of the peptide mode of action probably involves formation of peptide assemblies (possibly membrane pores), which disrupt bacterial membrane and, consequently, allow membrane penetration.
我们研究了与各种膜模拟模型相互作用时与抗菌肽 Halictine-1 (HAL-1) 相关的肽的结构变化，目的是确定肽作用模式的机制，并找到一级/二级结构变化与生物学活性之间的相关性。在特定位置对 HAL-1 氨基酸序列进行修饰，增加两亲性（Arg/Lys 交换）、限制流动性（插入 Pro），导致抗菌和溶血活性的变化，导致对模型膜的不同行为。通过圆二色性、红外光谱和荧光光谱研究了肽-膜相互作用引起的二级结构变化。实验结果通过分子动力学计算得到补充。发现 α-螺旋结构对于 HAL-1 肽的抗菌作用是必要的，但不是完全充分的。替代构象（如β-折叠、PPII 或 3-螺旋）的作用似乎也很重要。肽作用模式的机制可能涉及肽组装（可能是膜孔）的形成，这些组装破坏细菌膜，从而允许膜穿透。
