The Molecular Basis for Antimicrobial Activity of Pore-Forming Cyclic Peptides
The Molecular Basis for Antimicrobial Activity of Pore-Forming Cyclic Peptides
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DOI：
10.1016/j.bpj.2011.03.057
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发表时间：
2011-05-18
影响因子：
3.4
通讯作者：
Sengupta, Durba
中科院分区：
文献类型：
--
作者：
Cirac, Anna D.;Moiset, Gemma;Sengupta, Durba
据我们所知，抗菌肽的作用机制仍然知之甚少。为了探索赋予活性的生物物理特性，我们在这里提出了一个环状抗菌肽及其无活性线性类似物的分子动力学和生物物理研究。在模拟中，环肽在双层中引起大的扰动，并协同打开直径为1-2 nm的无序环形孔。电生理学测量证实了大小相当的离散穿孔事件。我们还表明，赖氨酸残基对齐彼此平行的环状肽，而不是线性肽的功能是至关重要的。通过采用双色荧光猝发分析，我们表明，这两种肽都能够融合/聚集脂质体，但只有环肽能够穿孔。结果提供了详细的洞察力的活性的环状抗菌肽的分子基础。
The mechanism of action of antimicrobial peptides is, to our knowledge, still poorly understood. To probe the biophysical characteristics that confer activity, we present here a molecular-dynamics and biophysical study of a cyclic antimicrobial peptide and its inactive linear analog. In the simulations, the cyclic peptide caused large perturbations in the bilayer and cooperatively opened a disordered toroidal pore, 1-2 nm in diameter. Electrophysiology measurements confirm discrete poration events of comparable size. We also show that lysine residues aligning parallel to each other in the cyclic but not linear peptide are crucial for function. By employing dual-color fluorescence burst analysis, we show that both peptides are able to fuse/aggregate liposomes but only the cyclic peptide is able to porate them. The results provide detailed insight on the molecular basis of activity of cyclic antimicrobial peptides.