Mammalian iron-sulfur cluster biogenesis

哺乳动物铁硫簇生物发生

• 批准号: 7594264
• 负责人: TRACEY A. ROUAULT
• 金额: $ 86.37万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7594264
• 关键词: Aconitate Hydratase; Apoproteins; Binding; Biogenesis; Cell Nucleus; Cells; Citric Acid Cycle; Cytosol; Disease; Enzymes; Friedreich Ataxia; Genes; Goals; Homeostasis; Iron; Iron-Sulfur Proteins; Mammalian Cell; Mitochondria; Mutagenesis; Pathogenesis; Prosthesis; Proteins; RNA Binding; RNA-Binding Proteins; Regulation; Role; Sideroblastic Anemia; Sulfur; Sulofenur

IRP1 is an iron-sulfur protein related to mitochondrial aconitase, a citric acid cycle enzyme, and it functions as a cytosolic aconitase in cells that are iron replete. Regulation of RNA binding activity of IRP1 involves a transition from a form of IRP1 in which a 4Fe-4S cluster is bound, to a form that loses both iron and aconitase activity. The 4Fe-4S containing protein does not bind IREs. Controlled degradation of the iron-sulfur cluster and mutagenesis reveals that the physiologically relevant form of the RNA binding protein in iron-depleted cells is apoprotein. The status of the cluster appears to determine whether IRP1 will bind RNA. Recently, we have identified mammalian enzymes of iron-sulfur cluster assembly that are homologous to the NifS, ISCU and Nif U genes implicated in bacterial iron-sulfur cluster assembly, and we have shown that these gene products facilitate assembly of the iron- sulfur cluster of IRP1.

IRP 1是一种与线粒体顺乌头酸酶（一种柠檬酸循环酶）相关的铁硫蛋白，它在铁充足的细胞中发挥细胞质顺乌头酸酶的作用。IRP 1的RNA结合活性的调节涉及从其中结合4Fe-4S簇的IRP 1形式转变为失去铁和顺乌头酸酶活性的形式。含有4Fe-4S的蛋白质不结合IRE。铁-硫簇的受控降解和诱变揭示了铁耗竭细胞中RNA结合蛋白的生理相关形式是脱辅基蛋白。簇的状态似乎决定了IRP 1是否会结合RNA。最近，我们已经鉴定了与细菌铁硫簇组装中涉及的NifS、ISCU和Nif U基因同源的铁硫簇组装的哺乳动物酶，并且我们已经表明这些基因产物促进IRP 1的铁硫簇的组装。