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Development of Sensor System to Analyse and Diagnose the abnormality of Protein Conformation

蛋白质构象异常分析诊断传感器系统的开发

基本信息

批准号：
15206089
负责人：
KUBOI Ryoichi
金额：
$ 27.96万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
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

项目摘要

The goal of this research project is to establish the analytical method of dynamic interaction between the structurally abnormal protein and biomembrane under the stress condition, especially focusing on the local hydrophobicity (LH) or structural fluctuation. Amyloid beta peptide (Aβ) has been employed as a case study of the system to analyze and characterize the structural abnormality of various proteins. During past two years, we have developed the sensor system of the structural abnormality of protein and have established the database on the protein abnormality under the stress condition. In 2005, the method to judge the structural abnormality of proteins has been investigated based on the previous findings. Based on the database, the suitable conditions (stress condition and lipid compositions) to regenerate the conformational abnormality of protein under the stress condition on the liposome surface have been clarified, resulting that the microdomain-like structure of the membrane … More surface was found to play an important role on the conformational abnormality of proteins/peptides. It was furthermore found that the microdomain-like structure could suitably be controlled by the control of the stress conditions (heating, pH and ionic strength) and the modification of membrane components (alcohols, fatty acids, cholesterol). Especially in the case of the cholesterol-modified liposome, the Aβ-membrane interaction was found to be controlled on the membrane in the presence of metal ion, Cu. The Aβ-Cu complex furthermore induced the metalloenzyme-like function(oxidation of cholesterol and dopamine). The above potential functions of Aβ on the membrane was found to be closely related to the stability of hydrogen-bond of the main chain of the Aβ in the hydrophobic nano environment inside the liposome membrane. By using the membrane chip arraying various stressed-liposomes on the chip, it was found that we could assess the structural abnormality of the protein. The above findings on the structural abnormality of protein were summarized together with the physiological role of amyloid fibril formation of Aβ on the biomembrane. Less

本研究的目的是建立应力条件下结构异常蛋白质与生物膜动态相互作用的分析方法，特别是研究局部疏水性（LH）或结构波动。以淀粉样β肽（Aβ）为例，分析和表征了各种蛋白质的结构异常。在过去的两年中，我们开发了蛋白质结构异常的传感器系统，并建立了应激条件下蛋白质异常的数据库。2005年，基于以前的发现，研究了判断蛋白质结构异常的方法。基于该数据库，阐明了在脂质体表面应力条件下蛋白质构象异常再生的适宜条件（应力条件和脂质组成），导致膜的微区样结构 ...更多信息发现表面对蛋白质/肽的构象异常起重要作用。此外还发现，微区状结构可以通过控制应力条件（加热、pH和离子强度）和膜组分（醇、脂肪酸、胆固醇）的改性来适当地控制。特别是在胆固醇修饰的脂质体的情况下，发现在金属离子Cu存在下，Aβ-膜相互作用在膜上被控制。Aβ-Cu复合物还诱导了类金属酶功能（胆固醇和多巴胺的氧化）。发现Aβ在膜上的上述潜在功能与Aβ主链上的氢键在脂质体膜内的疏水纳米环境中的稳定性密切相关。通过使用在芯片上排列各种应激脂质体的膜芯片，发现我们可以评估蛋白质的结构异常。总结了上述关于蛋白质结构异常的发现，以及Aβ在生物膜上形成淀粉样纤维的生理作用。少