Dynamic structure of intermedilysin : Analysis of membrane binding region

背景：中间溶血素(Intermedilysin，ILY)是一种由中间链球菌分泌的人类特异性溶细胞素。在本研究中，我们分析了ILY、链球菌溶血素O(SLO)及其12聚体取代突变体在500ps内的动态结构。通过对偶极矩、静电势等参数的测定，探讨了膜结合的分子机制。材料与方法：利用同源模块InsightII-Discover构建了ILY、SLO及其突变体的分子模型。用Discover3模块模拟分子动力学，提取膜结合12聚体区域的z矩阵数据，计算分子轨道参数(偶极矩、溶剂化自由能)。结果：溶细胞素呈弓形振动，ILY 12聚体区域的偶极矩方向与SLO不同。某些ILY突变体表现出类SLO偶极性质，具有SLO型11聚半胱氨酸基序氨基酸序列。ILY 11mer区比SLO区疏水性更强，似乎更容易与无胆固醇的细胞膜相互作用。ILY和SLO的静电场分布不同，特别是在11聚体区域。结论：在11聚体区域，这些细胞溶血素的偶极矩方向在分子运动过程中是恒定的，并且可以与各种类型的膜成分(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.