不同环境下帕金森病相关的α-突触核蛋白与synaptobrevin-2相互作用的核磁共振波谱研究

项目名称： 不同环境下帕金森病相关的α-突触核蛋白与synaptobrevin-2相互作用的核磁共振波谱研究

项目编号： No.21203243

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 物理化学

项目作者： 张则婷

作者单位： 中国科学院武汉物理与数学研究所

项目金额： 27万元

中文摘要： 蛋白质相互作用是细胞中功能调控的基础，研究与疾病相关蛋白质之间的相互作用对了解疾病的发生发展具有重要意义。α-syn为天然无序蛋白，在不同环境下存在结构差异。研究表明，α-syn可与synaptobrevin-2（syb2）发生相互作用参与神经递质释放调节，该过程与帕金森病发生密切相关，然而α-syn与syb2相互作用的分子机制目前尚不清楚。本项目将采用核磁共振波谱技术分别在水环境、膜环境以及细胞内拥挤环境中研究α-syn与syb2的相互作用。具体包括：1.分析相互作用是否依赖于环境诱导的蛋白结构；2.比较不同环境中相互作用的热力学性质；3.探究相互作用界面。通过本项目的研究探寻环境效应对天然无序蛋白相互作用的影响，研究结果将对揭示α-syn与syb2在细胞中相互作用的分子机制、了解α-syn调节神经递质释放机理以及研究帕金森病致病过程都有重要意义。

中文关键词： α-syn；syb2；相互作用；膜环境；磷酸化修饰

英文摘要： Protein-protein interactions are the basis of functional regulations in cells. It's significant to study the interactions of the proteins for the knowledge of the occurrence and development of relevant disease. α-syn is an intrinsically disordered protein, which has different conformations in different environments. Recent observations indicated that α-syn participate in the regulation of neurotransmitter release through directly binding to synaptobrevin-2 （syb2）, and this process is closely related to Parkinson's disease. However, the molecular mechanism of the interaction between α-syn and syb2 is unknown till now. This project is going to investigate the interaction between α-syn and syb2 in different environments, including in aqueous buffer, in membranes and in cells using the nuclear magnetic resonance (NMR) spectroscopy, and will reveal the relationship of the protein interactions and protein conformations in different environments. Furthermore, the thermodynamic property and the binding surface involved in the interaction between these two proteins will also be studied. Through this project, we will explore the role of the environment in the interactions between intrinsically disordered proteins. This research will reveal the molecular mechanism of the interaction between α-syn and syb2, and make knowled

英文关键词： α-syn；syb2；interaction；membrane；phosphorylation