STRUCTURAL STUDIES OF AAA ATPASES

AAA ATP酶的结构研究

• 批准号: 8361064
• 负责人: Francis T.F. Tsai
• 金额: $ 1.23万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361064
• 关键词: ATP phosphohydrolase; Alzheimer' s Disease; Binding; Biological Process; Chemicals; Dissociation; Electron Microscopy; Family; Funding; Goals; Grant; Heat shock proteins; Homologous Gene; Hydrolysis; Infection; Mechanics; Mediating; Molecular Chaperones; Molecular Weight; National Center for Research Resources; Peptide Hydrolases; Principal Investigator; Prions; Proteins; Research; Research Infrastructure; Resources; Source; Structure; United States National Institutes of Health; Work; Yeasts; cost; human disease; macromolecule; member; protein aggregate; protein aggregation; protein misfolding

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 蛋白质必须正确折叠才能实现生物学功能。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 如阿尔茨海默病和朊病毒介导的感染。与其他更传统的 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) 具有从先前的蛋白质中拯救蛋白质的非凡能力。 聚合状态。 ClpB/Hsp104 家族的成员形成六聚环结构 分子量约为 600 kDa，可转换来自 ATP 结合的化学能和 ? 水解成机械功。这项研究的目的是提供详细的 了解 ClpB 和 Hsp104 如何促进先前解离的机制 聚集的蛋白质。我们建议使用冷冻电镜来研究它们的结构。