STRUCTURE - FUNCTION AND KINETICS OF AAA+ ATPASES

AAA 腺苷酸酶的结构 - 功能和动力学

• 批准号: 7601770
• 负责人: B TRACY NIXON
• 金额: $ 2.94万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601770
• 关键词: ATP Hydrolysis; ATP phosphohydrolase; Address; Cell division; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA-Directed RNA Polymerase; Data; Data Collection; Defect; Disease; Funding; Gene Expression; Genetic Transcription; Goals; Grant; Human; Hydrogen; Institution; Kinetics; Mechanics; Membrane; Molecular Machines; Nitrogen Fixation; Organelles; Production; Proteins; Research; Research Personnel; Resources; Rest; Schedule; Source; Structure; United States National Institutes of Health; Variant; Work; chromatin remodeling; data structure; enhancer binding protein; mutant; novel; pathogen; promoter; remediation; repaired; research study

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. Why do defects in molecular machines (AAA+ ATPases) cause disease? These protein machines convert ATP hydrolysis into mechanical work. Both human cells and disease causing pathogens use this work to physically manipulate proteins or DNA to dismantle and reassemble membranes or other organelles, to replicate DNA and traverse cell division, to repair damaged proteins, or to regulate gene expression. We do not know how these molecular machines convert ATP hydrolysis into mechanical work. Our research focuses on one subset of AAA+ ATPAses, the bacterial-enhancer-binding proteins (EBPs) which use their ATPase activities to regulate transcription of genes needed for harmful activites (diseases, crop damage) or helpful ones (nitrogen fixation, environmental remediation, hydrogen or other metabolite production). In a prior project, we established two mechanisms for regulating the EBP ATPases, and began defining structural changes occuring in their catalytic cycle. The current project completes this latter goal and extends it to address the underlying mechanism via structure function studies of mutant forms of ATPase. Initial data for mutant proteins were collected, with final data collection scheduled for March of 2007. In addition, in 2006 data were collected for a novel complex of ATPase and its target protein (the s54 subunit of RNA polymerase), and control experiments for contrast variation SANS observations of complexes of promoter DNA with s54, s54 and ATPase, or s54, ATPase and the rest of RNA polymerase. Finally, preliminary data for structures of two additional EBP proteins and a eukaryotic chromatin remodeling protein were obtained.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 为什么分子机器（AAA+ ATPases）的缺陷会导致疾病？这些蛋白质机器将ATP水解转化为机械工作。引起病原体的人类细胞和疾病都使用这项工作来物理操纵蛋白质或DNA来拆除并重新组装膜或其他细胞器，以复制DNA和遍及细胞分裂，以修复受损的蛋白质，或调节基因表达。我们不知道这些分子机器如何将ATP水解转化为机械工作。我们的研究重点是AAA+ ATPases的一个子集，即细菌 - 增强剂结合蛋白（EBP），这些蛋白（EBP）使用其ATPase活动来调节有害活动物所需的基因转录（疾病，作物损害）或有帮助的基因（氮固定，环境修复，氢化，氢化，氢或其他代谢产物）。 在先前的项目中，我们建立了两种调节EBP ATPases的机制，并开始定义其催化周期中发生的结构变化。当前的项目完成了后一个目标，并将其扩展到通过ATPase突变形式的结构功能研究来解决基本机制。收集了突变蛋白的初始数据，最终数据收集计划于2007年3月进行。此外，在2006年收集了一种数据，用于新型ATPase及其靶蛋白（RNA聚合酶的S54亚基）的新型复合物，以及对照实验的对照实验，以进行对比度变化与S54和S54，S54和S54，S54和Atpase的复合物的对比度变化，或者S54和Atep的综合体，或聚合酶。最后，获得了另外两种EBP蛋白结构和真核染色质重塑蛋白的初步数据。