Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Marburg, Germany.
Nat Chem Biol. 2010 Oct;6(10):758-65. doi: 10.1038/nchembio.432. Epub 2010 Aug 29.
Cytosolic and nuclear iron-sulfur (Fe-S) proteins play key roles in processes such as ribosome maturation, transcription and DNA repair-replication. For biosynthesis of their Fe-S clusters, a dedicated cytosolic Fe-S protein assembly (CIA) machinery is required. Here, we identify the essential flavoprotein Tah18 as a previously unrecognized CIA component and show by cell biological, biochemical and spectroscopic approaches that the complex of Tah18 and the CIA protein Dre2 is part of an electron transfer chain functioning in an early step of cytosolic Fe-S protein biogenesis. Electrons are transferred from NADPH via the FAD- and FMN-containing Tah18 to the Fe-S clusters of Dre2. This electron transfer chain is required for assembly of target but not scaffold Fe-S proteins, suggesting a need for reduction in the generation of stably inserted Fe-S clusters. The pathway is conserved in eukaryotes, as human Ndor1-Ciapin1 proteins can functionally replace yeast Tah18-Dre2.
细胞质和核内铁硫（Fe-S）蛋白在核糖体成熟、转录和 DNA 修复复制等过程中发挥着关键作用。为了合成其 Fe-S 簇，需要一种专门的细胞质 Fe-S 蛋白组装（CIA）机制。在这里，我们鉴定出必需的黄素蛋白 Tah18 作为一个以前未被识别的 CIA 组成部分，并通过细胞生物学、生化和光谱学方法表明，Tah18 和 CIA 蛋白 Dre2 的复合物是在细胞质 Fe-S 蛋白生物发生的早期步骤中起作用的电子传递链的一部分。电子从 NADPH 通过含有 FAD 和 FMN 的 Tah18 转移到 Dre2 的 Fe-S 簇。这个电子传递链对于靶但不是支架 Fe-S 蛋白的组装是必需的，这表明需要减少稳定插入的 Fe-S 簇的生成。该途径在真核生物中是保守的，因为人类 Ndor1-Ciapin1 蛋白可以在功能上替代酵母 Tah18-Dre2。
