Acidic residues of yeast frataxin have an essential role in Fe-S cluster assembly
Acidic residues of yeast frataxin have an essential role in Fe-S cluster assembly
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DOI：
10.1038/sj.embor.7400881
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发表时间：
2007-02-01
期刊：
影响因子：
7.7
通讯作者：
Trincal, Mathieu
中科院分区：
文献类型：
--
作者：
Foury, Francoise;Pastore, Annalisa;Trincal, Mathieu
弗里德赖希共济失调是由共济失调蛋白水平降低引起的，共济失调蛋白是一种线粒体酸性蛋白，被认为在支架Isu蛋白上的Fe-S簇组装中充当伴侣。Frataxin具有体外形成铁负载多聚体的能力，这也表明了铁储存功能。据报道，丙氨酸取代酵母frataxin（Yfh 1）的酸性脊的残基在体外eliminate铁结合的损失，但没有影响在体内Fe-S簇的合成。在这里，我们表明，一个显着的变化，在静电特性的一个特定区域的Yfh 1表面-通过取代两个或四个酸性残基由赖氨酸或丙氨酸，分别损害Fe-S簇组装，削弱Yfh 1和Isu 1之间的相互作用，并增加氧化损伤。因此，酸性脊对于Yfhl功能是必不可少的，并且可能参与铁介导的蛋白质-蛋白质相互作用。
Friedreich ataxia is caused by decreased levels of frataxin, a mitochondrial acidic protein that is assumed to act as chaperone in the assembly of Fe-S clusters on the scaffold Isu protein. Frataxin has the in vitro capacity to form iron-loaded multimers, which also suggests an iron storage function. It has been reported that alanine substitution of residues in an acidic ridge of yeast frataxin (Yfh1) elicits loss of iron binding in vitro but has no effect on Fe-S cluster synthesis in vivo. Here, we show that a marked change in the electrostatic properties of a specific region of Yfh1 surface-by substituting two or four acidic residues by lysine or alanine, respectively-impairs Fe-S cluster assembly, weakens the interaction between Yfh1 and Isu1, and increases oxidative damage. Therefore, the acidic ridge is essential for the Yfhl function and is likely to be involved in iron-mediated protein-protein interactions.