STRUCTURAL STUDIES OF AAA ATPASES

AAA ATP酶的结构研究

• 批准号: 8168534
• 负责人: Francis T.F. Tsai
• 金额: $ 2.15万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-15 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168534
• 关键词: ATP phosphohydrolase; Alzheimer' s Disease; Binding; Biological Process; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Dissociation; Family; Funding; Goals; Grant; Heat shock proteins; Homologous Gene; Hydrolysis; Infection; Institution; Mechanics; Mediating; Molecular Chaperones; Molecular Weight; Peptide Hydrolases; Prions; Proteins; Research; Research Personnel; Resources; Source; Structure; United States National Institutes of Health; Work; Yeasts; human disease; member; protein aggregate; protein aggregation

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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不同，酪蛋白分解蛋白酶 B (ClpB) 及其酵母同源热休克蛋白 104 (Hsp104) 具有将蛋白质从先前聚集状态中拯救出来的卓越能力。 ClpB/Hsp104 家族的成员形成分子量约为 600 kDa 的六聚环结构，并将 ATP 结合和水解产生的化学能转化为机械功。本研究的目的是提供 ClpB 和 Hsp104 如何促进先前聚集的蛋白质解离的详细机制。我们建议使用冷冻电镜来研究它们的结构。