Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p
Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p
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DOI：
10.1093/emboj/cdg446
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发表时间：
2003-09-15
期刊：
影响因子：
11.4
通讯作者：
Lill, R
中科院分区：
文献类型：
--
作者：
Mühlenhoff, U;Gerber, J;Lill, R
真核生物线粒体蛋白Isu1p和Isu2p在细胞铁硫（Fe/S）蛋白成熟过程中起重要作用。通过用Fe-55对酵母细胞进行放射性标记，我们证明了Isu1p结合了一个耐氧的不可螯合的Fe/S簇，这为Isu1p在Fe/S簇组装过程中的支架功能提供了体内证据。调控基因表达导致半胱氨酸脱硫酶Nfs1p、铁氧化还蛋白Yah1p或酵母精蛋白同源物Yfh1p的耗损，导致Isu1p上Fe/S簇的重新合成强烈减少。相比之下，Hsp70伴侣Ssq1p、其共同伴侣Jac1p或glutaredoxin Grx5p的缺失显著增加了与Isu1p结合的铁/S簇的数量，尽管这些线粒体蛋白对铁/S蛋白的成熟至关重要。因此，Ssq1p/Jac1p和Grx5p在Isu1p上合成铁/S簇后的一个步骤中是必需的，例如从Isu1p上解离预组装的铁/S簇和/或将其插入载脂蛋白中。我们提出了一个模型，该模型将Fe/S簇生物发生分解为两个主要步骤，并将其核心成分分配给这两个步骤中的一个。
The mitochondrial proteins Isu1p and Isu2p play an essential role in the maturation of cellular iron-sulfur (Fe/S) proteins in eukaryotes. By radiolabelling of yeast cells with Fe-55 we demonstrate that Isu1p binds an oxygen-resistant non-chelatable Fe/S cluster providing in vivo evidence for a scaffolding function of Isu1p during Fe/S cluster assembly. Depletion of the cysteine desulfurase Nfs1p, the ferredoxin Yah1p or the yeast frataxin homologue Yfh1p by regulated gene expression causes a strong decrease in the de novo synthesis of Fe/S clusters on Isu1p. In contrast, depletion of the Hsp70 chaperone Ssq1p, its co-chaperone Jac1p or the glutaredoxin Grx5p markedly increased the amount of Fe/S clusters bound to Isu1p, even though these mitochondrial proteins are crucial for maturation of Fe/S proteins. Hence Ssq1p/Jac1p and Grx5p are required in a step after Fe/S cluster synthesis on Isu1p, for instance in dissociation of preassembled Fe/S clusters from Isu1p and/or their insertion into apoproteins. We propose a model that dissects Fe/S cluster biogenesis into two major steps and assigns its central components to one of these two steps.