谷胱甘肽化修饰对Hsp70家族分子伴侣功能的影响

项目名称： 谷胱甘肽化修饰对Hsp70家族分子伴侣功能的影响

项目编号： No.31270794

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 张红

作者单位： 中国科学院生物物理研究所

项目金额： 80万元

中文摘要： 蛋白质巯基的谷胱甘肽化修饰参与动植物多种生理活动的精细调节。Hsp70家族分子伴侣（Hsp70s）作为生命必需的分子伴侣，在细胞活动的多领域都有影响，被誉为"分子超级工具"。Hsp70s的谷胱甘肽化修饰已在多种细胞的氧化应激条件下被检测到，然而谷胱甘肽化修饰对Hsp70s的结构和功能的影响及其细胞效应仍然鲜有研究数据。本项目将致力于体外研究Hsp70s发生谷胱甘肽化修饰的基本条件、反应机制及去谷胱甘肽化的酶促催化反应，重点研究谷胱甘肽化修饰对Hsp70s结构的扰动及对其ATPase活性和分子伴侣功能的影响，进一步研究细胞内Hsp70s发生谷胱甘肽化修饰的促发因素和后续生理效应，阐述Hsp70s发生谷胱甘肽化修饰前后的系列生化事件。本项目成果将为Hsp70s功能的调节机制提供新思路，并为谷胱甘肽化修饰研究提供基础数据。

中文关键词： 热休克蛋白70；谷胱甘肽化；结构；功能；

英文摘要： Glutathionylation of cysteine residues plays an important role in fine-tuning the regulation of proteins involved in diverse physiological functions in animal and plant cells. Hsp70 chaperones, which are essential for cell survival, take part in a wide range of cellular activities, so have earned the name "molecular supertool" . Glutathionylation of Hsp70 proteins has been detected in several different types of cells under conditions of oxidative stress. However, there is still little information available about the effects of glutathionylation on the structure and function of Hsp70 proteins, or the resulting physiological consequences. This study will focus on in vitro investigation of the conditions required for glutathionylation of Hsp70 proteins to occur, the mechanism of the reaction, and the mechanism of the emzymatically-catalysed degluthionylation reaction. In particular, we will investigate the effect of glutathionylation on the structure of Hsp70 proteins, and how this affects their ATPase and chaperone activities. In addition, we will investigate what factors are able to trigger glutathionylation of Hsp70 proteins in the cell and the consequences of this. This work will provide an integrated picture of the biochemical events before and after Hsp70 glutathionylation. The results will shed new light on

英文关键词： Hsp70；glutathionylation；structure；function；