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

该研究项目的目的是在应力条件下建立结构异常蛋白质和生物膜之间动态相互作用的分析方法，尤其是专注于局部疏水性（LH）或结构波动。淀粉样蛋白β（Aβ）已被用作系统的案例研究，以分析和表征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绝对性的传感器系统，并在应力条件下建立了有关蛋白质异常的数据库。 2005年，根据先前的发现，已经研究了判断蛋白质结构异常的方法。基于数据库，已经阐明了合适的条件（应力条件和脂质组成），以再生在脂质体表面的应力条件下蛋白质的构象异常，从而导致膜的微域样结构……更表面在蛋白蛋白/peptides的蛋白蛋白/peptides会议上起重要作用。此外，发现类似微区的结构可以通过控制应力条件（加热，pH和离子强度）以及膜成分（醇，脂肪酸，胆固醇）的修饰来适当控制。特别是在胆固醇修饰的脂质体的情况下，发现在金属离子存在Cu的情况下，Aβ-膜相互作用在膜上受到控制。 Aβ-CU复合物还诱导了金属酶样功能（胆固醇和多巴胺的氧化）。发现Aβ在膜上的上述电势功能与脂质体膜内疏水性纳米环境中Aβ主链的氢键的稳定性密切相关。通过在芯片上使用各种应力 - 脂质体的膜芯片，发现我们可以评估蛋白质的结构异常。上述关于蛋白质结构异常的发现与Aβ在生物膜上的淀粉样蛋白原纤维形成的物理作用进行了总结。较少的