对于在Isu1上进行铁硫簇合成至关重要的，铁调素与Isu1/Nfs1之间的相互作用。
An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1.
作者信息
Gerber Jana, Mühlenhoff Ulrich, Lill Roland
机构信息
Institute for Cytobiology and Cytopathology, Philipps-Universität Marburg, Robert-Koch Strasse 6, D-35033 Marburg, Germany.
出版信息
EMBO Rep. 2003 Sep;4(9):906-11. doi: 10.1038/sj.embor.embor918. Epub 2003 Aug 15.
Abstract
Depletion of the mitochondrial matrix protein frataxin is the molecular cause of the neurodegenerative disease Friedreich ataxia. The function of frataxin is unclear, although recent studies have suggested a function of frataxin (yeast Yfh1) in iron/sulphur (Fe/S) protein biogenesis. Here, we show that Yfh1 specifically binds to the central Fe/S-cluster (ISC)-assembly complex, which is composed of the scaffold protein Isu1 and the cysteine desulphurase Nfs1. Association between Yfh1 and Isu1/Nfs1 was markedly increased by ferrous iron, but did not depend on ISCs on Isu1. Functional analyses in vivo showed an involvement of Yfh1 in de novo ISC synthesis on Isu1. Our data demonstrate a crucial function of Yfh1 in Fe/S protein biogenesis by defining its function in an early step of this essential process. The iron-dependent binding of Yfh1 to Isu1/Nfs1 suggests a role of frataxin/Yfh1 in iron loading of the Isu scaffold proteins.
摘要
线粒体基质蛋白frataxin的缺失是神经退行性疾病弗里德赖希共济失调的分子病因。尽管最近的研究表明frataxin（酵母Yfh1）在铁/硫（Fe/S）蛋白生物合成中发挥作用，但其功能尚不清楚。在此，我们表明Yfh1特异性结合由支架蛋白Isu1和半胱氨酸脱硫酶Nfs1组成的中央Fe/S簇（ISC）组装复合物。亚铁可显著增强Yfh1与Isu1/Nfs1之间的结合，但不依赖于Isu1上的ISC。体内功能分析表明Yfh1参与了Isu1上从头合成ISC的过程。我们的数据通过定义Yfh1在这一关键过程早期步骤中的功能，证明了其在Fe/S蛋白生物合成中的关键作用。Yfh1与Isu1/Nfs1的铁依赖性结合表明frataxin/Yfh1在Isu支架蛋白的铁负载中发挥作用。
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