Correlation between single-molecule dynamics and biological functions of antimicrobial peptide melittin
Correlation between single-molecule dynamics and biological functions of antimicrobial peptide melittin
复制标题
抗菌肽蜂毒肽单分子动力学与生物学功能的相关性
DOI：
10.1021/acs.jpclett.0c01169
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发表时间：
2020
影响因子：
5.7
通讯作者：
Yuan Bing
中科院分区：
文献类型：
--
作者：
Xu Cheng;Ma Wendong;Wang Kang;He Kejie;Chen Zhonglan;Liu Jiaojiao;Yang Kai;Yuan Bing
许多基本的生物过程发生在细胞膜上，一个典型的例子是抗菌肽对细胞膜的渗透作用。以往对其机制的研究主要集中在膜和肽相互作用过程中的结构变化。本文从单分子动力学的新视角，实时监测了单个磷脂和肽分子的三维运动，并研究了它们与最具代表性的天然抗菌肽蜂毒蛋白的膜穿孔功能的相关性。我们发现蜂毒素在膜表面的吸附和积累显著加快了肽周围脂质的横向扩散，从而促进了肽在这些异质区域的插入。在膜插入过程中，蜂蜂素形成了独特的“U”型弯曲途径，并最终形成环形孔，在双层膜的两个小叶之间，多肽和脂质的动态易位具有几个亚稳态。
Many fundamental biological processes occur on cell membranes, and a typical example is the membrane permeabilization by peptides for an antimicrobial purpose. Previous studies of the underlying mechanism mostly focus on structural changes of membranes and peptides during their interactions. Herein, from a new perspective of single-molecule dynamics, the real-time three-dimensional motions of individual phospholipid and peptide molecules were monitored, and specifically, their correlation with the membrane poration function of melittin, a most representative natural antimicrobial peptide, was studied. We found that the adsorption and accumulation of melittin on the membrane surface significantly sped up the lateral diffusion of lipids surrounding the peptides, which in turn facilitated the peptide insertion at such heterogeneous regions. A unique “U”-bending pathway of melittin during membrane insertion and the ultimate formation of toroidal pores with dynamical translocations of peptides and lipids with several metastable states between the two leaflets of bilayer were observed.