STRUCTURAL AND FUNCTIONAL STUDIES ON IRON-SULFUR CLUSTER BIOGENESIS IN EUKARYOTE

真核生物中铁硫簇生物发生的结构和功能研究

• 批准号: 8170128
• 负责人: DAVID P BARONDEAU
• 金额: $ 0.58万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170128
• 关键词: Aconitate Hydratase; Apoproteins; Ataxia; Biogenesis; Cardiomyopathies; Cells; Cessation of life; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Defect; Diabetes Mellitus; Disease; Eukaryota; Ferritin; Friedreich Ataxia; Funding; Grant; Human; Impairment; Institution; Investigation; Iron; Length; Life; Link; Modeling; N-terminal; Neurologic; Oxidative Stress; Play; Proteins; Research; Research Personnel; Resources; Role; Scaffolding Protein; Set protein; Sideroblastic Anemia; Source; Sulfur; United States National Institutes of Health; Yeasts; cofactor; ferrochelatase; frataxin; heme biosynthesis; in vivo; protein complex; repaired

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. Iron-sulfur (Fe/S) clusters are important cofactors of numerous proteins. Fe/S clusters required a complex set of proteins to become assembled and incorporated into apoproteins in a living cell. The deficiency of Fe/S cluster proteins may cause cell malfunction and even death. In human, there are some diseases related to Fe/S cluster proteins such as X-linked sideroblastic anemia, X-linked sideroblastic anemia with ataxia and Friedreich ataxia. Frataxin, one of the Fe/S cluster assembly proteins has been the subject of intense investigation due to the discovery that frataxin defects are linked to Friedreich ataxia, a progressive disorder characterized by neurological impairment, cardiomyopathy, and diabetes. In vivo, frataxin promotes the biosynthesis of hemes by donating iron to ferrochelatase, the assembly of iron-sulfur clusters through interactions with the iron-sulfur scaffolding protein IscU, and the repair of iron-sulfur clusters such as aconitase. Frataxin also plays a primary role in the protection against oxidative stress. In yeast, Fe-dependent oligomerization of frataxin has been shown to form 24 subunit complexes that may function similarly to ferritin as iron-storage units. In human frataxin, N-terminal region is required for fratxin oligolmerization. Our results suggest that human frataxin forms larger (possibly 48 subunit) complexes. We have got the initial SAXS data for monomeric full-length human frataxin. The SAXS model suggests the extra N-terminal region might involve the interactions with IscU and frataxin oligomerization. We are trying to understand the interactions and functions of frataxin with IscU and IscS. We also like to investigate the protein complex of Fe/S cluster assembly machinery.

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表示。列出的机构是 对于中心，这不一定是调查员的机构。 铁硫（Fe/S）簇是许多蛋白质的重要​​辅助因子。 Fe/S簇需要一组复杂的蛋白质组装并掺入活细胞中的顶蛋白中。 Fe/S簇蛋白的缺乏可能会导致细胞功能故障甚至死亡。在人类中，有一些与Fe/S簇蛋白有关的疾病，例如X连锁的Sideroblastic贫血，X连锁的sideroblastic贫血与共济失调和Friedreich共济失调。 Frataxin是Fe/S簇组装蛋白之一，因为发现Frataxin缺陷与Friedreich共济失调有关，Friedreich ataxia是一种以神经系统障碍，心肌病和糖尿病为特征的进行性疾病，因此已经进行了严格的研究。在体内，frataxin通过将铁捐赠给铁铬酶，通过与铁 - 硫型支架蛋白ISCU的相互作用以及对铁硫簇（如抗刺激酶）的修复来促进HEMES的生物合成。 Frataxin在防止氧化应激中也起着主要作用。在酵母中，已证明Fe依赖性的frataxin的寡聚形成24个亚基复合物，这些复合物可能与铁蛋白一样起作用，就像铁储存单元一样。在人frataxin中，Fratxin寡酚需要N末端区域。我们的结果表明，人frataxin形成更大（可能是48个亚基）复合物。我们已经获得了单体全长人frataxin的初始SAXS数据。 SAXS模型表明，额外的N末端区域可能涉及与ISCU和Frataxin寡聚化的相互作用。我们正在尝试了解Frataxin与ISCU和ISC的相互作用和功能。我们还喜欢研究Fe/S簇组装机械的蛋白质复合物。