The Hsp90 molecular chaperone system

 描述(由申请人提供)：我们的长期目标是从生理相关性到机械作用来理解Hsp90分子伴侣系统。分子伴侣通常被认为是蛋白质生命周期的开始(折叠)和结束(降解)。然而，Hsp90系统中的伴侣通常与包括组装结构在内的天然蛋白质相关联。伴侣与看似天然的蛋白质相互作用的意义还知之甚少。我们将利用我们的发现，将Hsp90系统与染色质修饰物联系起来，以确定为什么某些伴侣与选定的天然蛋白质相互作用。我们目前的计划将解决分子伴侣如何协同调节多亚基蛋白质复合体。为了实现我们的目标，我们正在利用染色质重构体作为分子模型。简而言之，我们正在研究Hsp90和p23在核小体重塑过程中的单独和联合调节作用。我们的计划将定义Hsp90如何控制选择染色质重构体，将确定Hsp90和p23对染色质重构体的联合影响，将确定Hsp90对染色质景观的影响，并将展示Hsp90和p23对染色质重构体的控制如何支持动态平衡。

 DESCRIPTION (provided by applicant): Our long-term objectives are to understand the Hsp90 molecular chaperone system from physiological relevance to mechanistic action. Molecular chaperones are typically identified with the beginning (folding) and ending (degradation) of the protein life cycle. Yet, chaperones in the Hsp90 system are often associated with native proteins including assembled structures. The significance of chaperone interactions with seemingly native proteins is poorly understood. We will exploit our discoveries connecting the Hsp90 system to chromatin modifiers to determine why certain chaperones interact with select native proteins. Our current plans will resolve how molecular chaperones cooperatively modulate multi-subunit protein complexes. To achieve our goal we are exploiting chromatin remodelers as molecular models. In brief, we are investigating the individual and joint regulatory effects of Hsp90 and p23 on nucleosome remodeling process. Our plans will define how Hsp90 controls select chromatin remodelers, will identify the joint impact of Hsp90 and p23 on remodelers, will determine the impact of Hsp90 on the chromatin landscape, and will show how the control of chromatin remodelers by Hsp90 and p23 supports homeostasis.