The iron-binding CyaY and IscX proteins assist the ISC-catalyzed Fe-S biogenesis in Escherichia coli
The iron-binding CyaY and IscX proteins assist the ISC-catalyzed Fe-S biogenesis in Escherichia coli
复制标题
DOI：
10.1111/mmi.12888
复制
发表时间：
2015-02-01
影响因子：
3.6
通讯作者：
Py, Beatrice
中科院分区：
文献类型：
--
作者：
Roche, Beatrice;Huguenot, Allison;Py, Beatrice
在真核生物中，共济失调蛋白缺乏症（FXN）导致严重的表型，包括铁-硫（Fe-S）簇蛋白活性的丧失、线粒体铁的积累，并导致神经退行性疾病弗里德赖希共济失调。相反，在原核生物中，FXN同源物CyaY的缺乏据报道不会引起任何显著的表型，质疑其重要性及其对Fe-S簇生物发生的实际贡献。由于FXN在真核生物和原核生物之间是保守的，这种令人惊讶的差异促使我们重新研究CyaY在大肠杆菌中的作用。我们报告CyaY（i）增强大肠杆菌适应性，（ii）属于催化含Fe-S簇蛋白质成熟的ISC途径，（iii）需要富铁条件才能发挥重要作用。cyaY和isc操纵子的最后一个基因iscX之间存在遗传互作。这两个基因的缺失显示出对Fe-S簇蛋白成熟的累加效应，这导致对氨基糖苷类抗生素的抗性增加和对λ噬菌体感染的敏感性增加。总之，这些体内结果确立了CyaY作为大肠杆菌中ISC介导的Fe-S簇生物合成途径的成员的重要性，就像它在真核生物中一样，并验证了IscX作为一种新的真正的Fe-S簇生物合成因子。
In eukaryotes, frataxin deficiency (FXN) causes severe phenotypes including loss of iron-sulfur (Fe-S) cluster protein activity, accumulation of mitochondrial iron and leads to the neurodegenerative disease Friedreich's ataxia. In contrast, in prokaryotes, deficiency in the FXN homolog, CyaY, was reported not to cause any significant phenotype, questioning both its importance and its actual contribution to Fe-S cluster biogenesis. Because FXN is conserved between eukaryotes and prokaryotes, this surprising discrepancy prompted us to reinvestigate the role of CyaY in Escherichia coli. We report that CyaY (i) potentiates E.coli fitness, (ii) belongs to the ISC pathway catalyzing the maturation of Fe-S cluster-containing proteins and (iii) requires iron-rich conditions for its contribution to be significant. A genetic interaction was discovered between cyaY and iscX, the last gene of the isc operon. Deletion of both genes showed an additive effect on Fe-S cluster protein maturation, which led, among others, to increased resistance to aminoglycosides and increased sensitivity to lambda phage infection. Together, these in vivo results establish the importance of CyaY as a member of the ISC-mediated Fe-S cluster biogenesis pathway in E.coli, like it does in eukaryotes, and validate IscX as a new bona fide Fe-S cluster biogenesis factor.