Dynamic structure of intermedilysin : Analysis of membrane binding region

intermedilysin 的动态结构：膜结合区域分析

基本信息

批准号：
15590098
负责人：
OHKURA Kazuto
金额：
$ 2.3万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590098/
关键词：
infection cytolysin

项目摘要

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.

背景：Intermedilysin（Ily）是一种从Intermedius链球菌分泌的人类特异性细胞溶素。在这项研究中，我们分析了ILY，链霉素O（SLO）及其12mer取代突变体的动态结构。确定了几个参数，例如偶极矩和静电电位，以讨论膜结合的分子机制。材料和方法：使用与同源模块的Insighii-Discover构建ILY，SLO及其突变体的分子模型。使用Discover3模块模拟了它们的分子动力学，并提取膜结合12mer区域的Z-Matrix数据来计算MO参数（即偶极力矩，溶剂液压能（DGW））。结果：细胞素蛋白蛋白像弓形一样振动，像弓形一样振动，以及与Slo slo的二极管时刻的方向。某些ILY突变体表示Slo样偶极特性，其具有SLO型11mer半胱氨酸基序氨基酸序列。 ILY 11Mer区域比SLO的区域更疏水，并且似乎很容易与没有胆固醇的细胞膜相互作用。 ILY的静电电位场分布与SLO的静电场分布不同，尤其是在11Mer区域。结论：在11mer区域，这些细胞赛的偶极矩方向在分子运动过程中是恒定的，并且准备与膜成分（即胆固醇，磷脂）相互作用。