Dynamic structure of intermedilysin : Analysis of membrane binding region

intermedilysin 的动态结构：膜结合区域分析

• 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

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：中间溶素（intermediolysin，ILY）是由中间链球菌分泌的一种人特异性溶细胞素。本研究对ILY、链球菌溶血素O（Streptolysin O，SLO）及其12聚体置换突变体在500 ps内的动态结构进行了分析。材料与方法：利用InsightII-Discover软件，通过同源模块构建ILY、SLO及其突变体的分子模型。结果：溶细胞素呈弓形振动，ILY 12 mer区的偶极矩方向与SLO不同，其分子动力学参数为偶极矩、溶剂化自由能（dGW）。某些ILY突变体显示出SLO样偶极特性，其具有SLO型11聚体半胱氨酸基序氨基酸序列。ILY 11聚体区域比SLO区域更疏水，并且似乎在没有胆固醇的情况下更容易与细胞膜相互作用。结论：ILY和SLO在11 mer区域的静电势分布不同，在分子运动过程中，ILY和SLO的偶极矩方向是恒定的，可以与各种类型的膜组分（胆固醇、磷脂）相互作用。

项目成果

Intermedilysin is essential for the invasion of hepatoma HepG2 cells by Streptococcus intermedius

• DOI: 10.1111/j.1348-0421.2005.tb03647.x
• 发表时间: 2005-01-01
• 期刊: MICROBIOLOGY AND IMMUNOLOGY
• 影响因子: 2.6
• 作者: Sukeno, A;Nagamune, H;Kourai, H
• 通讯作者: Kourai, H

The Human-specific Action of Intermedilysin, a Homologue of Streptolysin O, is Dictated by Domain 4 of the Protein.

Intermedilysin（链球菌溶血素 O 的同源物）的人类特异性作用由该蛋白质的结构域 4 决定。

• 发表时间: 2004
• 期刊: Microbiol.Immunol. 48
• 作者: Nagamune;H.
• 通讯作者: H.

Ohkura, K.: "Analysis of Structural Features of Bis-Quaternary Ammonium Antimicrobial Agents 4,4'-α,ω-Polymethylenedithio)bis(1-alkylpyridinium lodide)s Using computational Simulation"Bioorganic & Medicinal Chemistry. 11. 5035-5043 (2003)

Ohkura, K.：“使用计算模拟分析双季铵抗菌剂 4,4-α,ω-聚亚甲基二硫基）双（1-烷基吡啶鎓碘）的结构特征”生物有机与药物化学 11. 5035-5043。 (2003)

A cell membrane modification technique using domain 4 of intermedilysin for immunotherapy against cancer

利用 intermedilysin 结构域 4 的细胞膜修饰技术用于癌症免疫治疗

• 发表时间: 2004
• 期刊: Anticancer Research Vol.24
• 作者: Hideaki Nagamune

The Human-specific Action of Intermedilysin, a Homologue of Streptolysin O, is Dictated by Domain 4 of the Protein

Intermedilysin（链球菌溶血素 O 的同源物）的人类特异性作用由蛋白质的结构域 4 决定

• 发表时间: 2004
• 期刊: Microbiology and Immunology Vol.48-No.9
• 作者: Hideaki Nagamune;Kazuto Ohkura;Akiko Sukeno;Graeme Cowan;Timothy J.Mitchell;Wataru Ito;Ooki Ohnishi;Kanako Hattori;Miki Yamato;Katsuhiko Hirota;Yoichiro Miyake;Takuya Maeda;Hiroki Kourai
• 通讯作者: Hiroki Kourai