STRUCTURAL STUDIES OF AAA ATPASES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 蛋白质必须正确折叠才能实现生物功能。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，如 阿尔茨海默氏症和普恩病毒介导的感染。不同于其他更传统的 分子伴侣、酪蛋白分解酶B(ClpB)及其酵母同系物热休克 蛋白质104(Hsp104)具有显著的拯救蛋白质的能力 聚合状态。ClpB/Hsp104家族成员形成六聚体环结构 ~600 kDa的相对分子质量，并转化来自于ATP结合的化学能和？ 将水解成机械功。这项研究的目的是提供一个详细的 从机制上理解ClpB和Hsp104如何促进以前的 聚集的蛋白质。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. 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.