STRUCTURAL STUDIES OF AAA ATPASES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 蛋白质必须正确折叠才能实现生物功能。与此同时，蛋白质聚集和错误折叠是许多毁灭性人类疾病的关键因素，例如阿尔茨海默病和普恩病毒介导的感染。与其他更传统的分子伴侣不同，酪蛋白水解酶B(ClpB)及其酵母同系物热休克蛋白104(Hsp104)具有从先前聚集的状态中拯救蛋白质的显著能力。ClpB/Hsp104家族的成员形成约600 kDa的六聚环结构，将ATP结合和水解产生的化学能转化为机械功。这项研究的目的是提供一个详细的机制了解ClpB和Hsp104如何促进先前聚集的蛋白质的解离。我们建议使用低温电子显微镜来研究它们的结构。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Proteins must fold correctly in order to attain biological function. Concurrently, protein aggregation and misfolding are key contributors to many devastating human diseases such as Alzheimer's disease and prion-mediated infections. Unlike other more conventional molecular chaperones, the caseinolytic protease B (ClpB) and its yeast homolog heat-shock protein 104 (Hsp104) have the remarkable ability to rescue proteins from a previously aggregated state. Members of the ClpB/Hsp104 family form hexameric ring structures of ~600 kDa in molecular weight and convert chemical energy derived from ATP-binding and hydrolysis into mechanical work. The goal of this research is to provide a detailed mechanistic understanding how ClpB and Hsp104 facilitate the dissociation of previously aggregated proteins. We propose to use cryo-EM to study their structures.