Dynamic structure of intermedilysin : Analysis of membrane binding region

背景：中间溶素（intermediilysin， ILY）是一种由中间链球菌分泌的人类特异性细胞溶素。在本研究中，我们分析了ILY、Streptolysin O （SLO）及其12个mer取代突变体在500ps期间的动态结构。测定了偶极矩和静电势等参数，探讨了膜结合的分子机制。材料与方法：使用insighi - discover软件，利用Homology模块构建ILY、SLO及其突变体的分子模型。利用Discover3模块模拟其分子动力学，提取膜结合12mer区域的z矩阵数据，计算MO参数（即偶极矩、溶剂化自由能（dGW））。结果：溶细胞素呈弓形振动，且iil12mer区偶极矩方向与SLO区不同。某些ILY突变体表现出类似slo的偶极子性质，具有slo型11聚半胱氨酸基序氨基酸序列。il11mer区比SLO区更疏水，似乎容易与无胆固醇的细胞膜相互作用。ILY的静电势场分布与SLO不同，特别是在11mer区域。结论：在11mer区，这些溶细胞素的偶极矩方向在分子运动过程中是恒定的，并且随时准备与每种类型的膜组分（如胆固醇、磷脂）相互作用。

Background : Intermedilysin (ILY) is a human-specific cytolysin secreted from Streptococcus intermedius. In this study, we analyzed the dynamic structure of ILY, Streptolysin O (SLO) and their 12mer substituted mutants during 500ps. Several parameters, such as dipole moment and electrostatic potential, were determined to discuss the molecular mechanism of membrane binding.Material and Methods : Molecular models of ILY, SLO and their mutants were constructed using InsightII-Discover with the Homology module. Their molecular dynamics were simulated with the Discover3 module, and z-matrix data of the membrane-binding 12mer region were extracted to calculate the MO parameters (i.e. dipole moment, solvation free energy (dGW)).Results : Cytolysins vibrated like a bow, and the dipole moment direction of ILY 12mer region was different from that of SLO. Certain ILY mutants indicated the SLO-like dipole properties, which had an SLO-type 11mer cysteine motif amino acid sequence. The ILY 11mer region was more hydrophobic than that of SLO, and seemed to easy interact with the cell membrane without cholesterol. The electrostatic potential field distribution of ILY differed from that of SLO, especially in the 11mer region.Conclusion : In the 11mer region, the dipole moment directions of these cytolysins were constant during molecular movement, and ready to interact with membrane components (i.e. cholesterol, phospholipid) in each style.