STRUCTURAL STUDIES OF AAA ATPASES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 蛋白质必须正确折叠以获得生物功能。同时，蛋白质聚集和错误折叠是许多破坏性人类疾病如阿尔茨海默病和朊病毒介导的感染的关键因素。与其他更常规的分子伴侣不同，酪蛋白分解蛋白酶B（Clp B）及其酵母同系物热休克蛋白104（Hsp 104）具有将蛋白质从先前聚集状态中拯救出来的显著能力。ClpB/Hsp 104家族的成员形成分子量约为600 kDa的六聚环结构，并转化来自ATP结合的化学能， 水解转化为机械功。本研究的目的是提供一个详细的机制，了解ClpB和Hsp 104如何促进先前聚集的蛋白质的解离。我们建议使用冷冻电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.