XAS CHARACTERIZATION OF FE SITES IN PROTEINS INVOLVED IN IRON HOMEOSTASIS & CELL

参与铁稳态的蛋白质中 FE 位点的 XAS 表征

• 批准号: 7370418
• 负责人: TIMOTHY Louis STEMMLER
• 金额: $ 0.49万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370418
• 关键词: XAS; CHARACTERIZATION; FE; SITES; PROTEINS

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. Although mitochondrial iron homeostasis is essential for cell viability, it is a mechanism that is poorly understood. Mitochondrial iron is required for heme and iron-sulfur cluster assembly and deficiency causes a collapse in metalloprotein biosynthesis, disrupting cellular pathways where enzymes that require these cofactors participate. However, overabundance of mitochondrial iron leads to oxidative stress in the cell, since iron is highly reactive. Cells have therefore developed protein controlled mechanisms to regulate mitochondrial iron concentrations at the level of metal import, export and possibly metal storage. Cellular respiration is controlled in the mitochondria by metalloproteins, so strict control of mitochondrial iron concentrations is essential for maintaining cell function and also to prevent metal toxicity. A goal of our lab is to characterize the function of two proteins involved in mitochondrial iron homeostasis and cellular respiration. Using XAS spectroscopy, we will characterize the iron active-site structure and reaction mechanism for these proteins to decipher their role in maintaining normal cellular function.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。尽管线粒体铁稳态对于细胞活力至关重要，但人们对这一机制知之甚少。线粒体铁是血红素和铁硫簇组装所必需的，缺乏会导致金属蛋白生物合成崩溃，破坏需要这些辅助因子的酶参与的细胞途径。然而，线粒体铁过多会导致细胞氧化应激，因为铁具有高度反应性。因此，细胞发展出了蛋白质控制机制，在金属输入、输出和可能的金属储存水平上调节线粒体铁浓度。细胞呼吸在线粒体中由金属蛋白控制，因此严格控制线粒体铁浓度对于维持细胞功能和防止金属毒性至关重要。我们实验室的目标是表征参与线粒体铁稳态和细胞呼吸的两种蛋白质的功能。利用 XAS 光谱，我们将表征这些蛋白质的铁活性位点结构和反应机制，以破译它们在维持正常细胞功能中的作用。