Regulation of iron-sulphur cluster homeostasis through transcriptional control of the Isc pathway by [2Fe-2S]-IscR in Escherichia coli.

Regulation of iron-sulphur cluster homeostasis through transcriptional control of the Isc pathway by [2Fe-2S]-IscR in Escherichia coli.
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DOI:
10.1111/mmi.12052
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发表时间:
2013-02
影响因子:
3.6
通讯作者:
Kiley PJ
Kiley PJ
中科院分区:
生物学2区
文献类型:
--
作者:
Giel JL;Nesbit AD;Mettert EL;Fleischhacker AS;Wanta BT;Kiley PJ

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Fe-S簇在整个生物世界中都是必不可少的,但细胞如何调节Fe-S簇生物发生途径的表达以应对Fe-S簇需求的变化尚不清楚。在这里,我们描述了大肠杆菌含有[2Fe-2S]簇的调节因子IscR调节Isc Fe-S生物发生途径的合成以维持Fe-S稳态的机制。我们的数据表明,一个负反馈回路通过将[2Fe-2S]-IscR结合到两个上游结合位点,抑制编码IscR和Isc机制的iscRSUA-hscBA-fdx操纵子的转录。研究表明,IscR主要需要Isc途径来合成其Fe-S簇,通过Isc系统的水平提供了IscR活性与Fe-S簇需求之间的联系。令人惊讶的是,在厌氧条件下,isc操纵子受到更大的抑制,这表明相对于好氧条件,IscR中Fe-S簇占用增加,Fe-S簇生物发生需求减少。与这一观点一致的是,在有氧条件下,而不是在厌氧条件下,Fe-S蛋白的过表达导致PiscR的抑制。总之,这些数据显示了[2Fe-2S]-IscR对iscRSUA-hscBA-fdx的转录控制如何使大肠杆菌有效地响应不同的Fe-S需求。
Fe-S clusters are essential across the biological world, yet how cells regulate expression of Fe-S cluster biogenesis pathways to cope with changes in Fe-S cluster demand is not well understood. Here, we describe the mechanism by which IscR, a [2Fe-2S] cluster-containing regulator of Escherichia coli, adjusts the synthesis of the Isc Fe-S biogenesis pathway to maintain Fe-S homeostasis. Our data indicate that a negative feedback loop operates to repress transcription of the iscRSUA-hscBA-fdx operon, encoding IscR and the Isc machinery, through binding of [2Fe-2S]-IscR to two upstream binding sites. IscR was shown to require primarily the Isc pathway for synthesis of its Fe-S cluster, providing a link between IscR activity and demands for Fe-S clusters through the levels of the Isc system. Surprisingly, the isc operon was more repressed under anaerobic conditions, indicating increased Fe-S cluster occupancy of IscR and decreased Fe-S cluster biogenesis demand relative to aerobic conditions. Consistent with this notion, overexpression of a Fe-S protein under aerobic conditions, but not under anaerobic conditions, led to derepression of PiscR. Together, these data show how transcriptional control of iscRSUA-hscBA-fdx by [2Fe-2S]-IscR allows E. coli to respond efficiently to varying Fe-S demands.
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