STRUCTURAL STUDIES OF AAA ATPASES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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毁灭性人类疾病的关键因素，例如 阿尔茨海默病和朊病毒介导的感染。与其他传统的 分子伴侣，酪蛋白分解蛋白酶B（Clp B）及其酵母同系物热激 蛋白104（Hsp 104）具有从先前的蛋白质中拯救蛋白质的显着能力。 聚合状态ClpB/Hsp 104家族的成员形成六聚体环结构， ~600 kDa的分子量和转换来自ATP结合和？ 水解转化为机械功。这项研究的目的是提供一个详细的 机制理解ClpB和Hsp 104如何促进先前的解离 聚集蛋白质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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.