STRUCTURE AND MECHANISTIC STUDIES OF HUMAN FE-S CLUSTER BIOSYNTHESIS

人类FE-S簇生物合成的结构与机制研究

• 批准号: 8362215
• 负责人: Chao-Ming Tsai
• 金额: $ 0.44万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362215
• 关键词: Anabolism; Ataxia; Binding Sites; Clinical; Complex; Funding; Grant; Homeostasis; Human; Inherited; Iron; Iron-Sulfur Proteins; National Center for Research Resources; Principal Investigator; Protein Biosynthesis; Proteins; Radiation; Research; Research Infrastructure; Resources; Scaffolding Protein; Source; Structure; Sulfur; United States National Institutes of Health; cost; frataxin; loss of function; mutant; structural biology

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. Friedreich?s ataxia is the most common inherited ataxia and results from the loss of function for the protein frataxin. Frataxin has been implicated in iron homeostasis and, particularly, in iron-sulfur protein biosynthesis. Frataxin specifically interacts with the scaffold protein IscU and delivers iron for iron-sulfur cluster assembly. Although the structure of human frataxin is known, the frataxin iron binding site, the structure of human IscU, and details for the frataxin:IscU complex remain elusive. In addition, clinical mutants of human frataxin have been identified (such as D122Y, G130V, I154F, W155R) but not structurally or functionally characterized. The objectives of this proposal are to determine crystallographic structures of (i) human frataxin with iron; (ii) clinical mutants of frataxin; (iii) human IscU; and (iv) the frataxin:IscU complex.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 弗里德赖希？共济失调是最常见的遗传性共济失调，并且是由蛋白共济失调蛋白的功能丧失引起的。Frataxin与铁稳态有关，特别是与铁硫蛋白的生物合成有关。Frataxin与支架蛋白IscU特异性相互作用，并为铁-硫簇组装提供铁。尽管已知人共济失调蛋白的结构，但共济失调蛋白铁结合位点、人IscU的结构以及共济失调蛋白：IscU复合物的细节仍然难以捉摸。此外，已经鉴定了人共济失调蛋白的临床突变体（如D122 Y、G130 V、I154 F、W155 R），但没有结构或功能表征。本提案的目的是确定（i）含铁的人共济失调蛋白;（ii）共济失调蛋白的临床突变体;（iii）人IscU;和（iv）共济失调蛋白：IscU复合物的晶体结构。