Sensing iron availability via the fragile [4Fe-4S] cluster of the bacterial transcriptional repressor RirA.
Sensing iron availability via the fragile [4Fe-4S] cluster of the bacterial transcriptional repressor RirA.
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DOI：
10.1039/c7sc02801f
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发表时间：
2017-12-01
期刊：
影响因子：
8.4
通讯作者：
Le Brun NE
中科院分区：
文献类型：
--
作者：
Pellicer Martinez MT;Martinez AB;Crack JC;Holmes JD;Svistunenko DA;Johnston AWB;Cheesman MR;Todd JD;Le Brun NE
铁的全局调节因子RirA通过与一个脆弱的[4Fe-4S]簇的结合来控制铁代谢基因的转录。根瘤菌铁调节因子A（Rhizobial iron regulator A，RirA）是一种全局性的铁稳态调节因子，存在于许多固氮根瘤菌和相关的α-变形菌中。它属于广泛分布的Rrf 2超家族的转录调节因子，具有三个保守的Cys残基，其抑制了其他Rrf 2家族调节因子中的铁硫簇的结合。在这里，我们报告的生物物理研究表明，RirA含有一个[4Fe-4S]簇，这种形式的蛋白质结合RirA调节的DNA，与其功能一致，作为一个阻遏物的表达，许多基因参与铁的吸收。在低铁条件下，[4Fe-4S] RirA经历簇转化反应，导致[2Fe-2S]形式，其对DNA表现出低得多的亲和力。在长时间的低铁条件下，[2Fe-2S]簇降解为apo-RirA，其不结合DNA，并且不再作为细胞铁吸收机制的阻遏物发挥作用。[4Fe-4S] RirA对O2敏感，表明铁和O2都是铁代谢的重要信号。与此相一致，体内数据表明，RirA调节基因的表达也受到O2的影响。这些数据使我们提出了一种新的铁稳态调控模型，其中RirA通过掺入对铁和O2浓度敏感的脆弱的铁硫簇来感知铁。
The global iron regulator RirA controls transcription of iron metabolism genes via the binding of a fragile [4Fe–4S] cluster. Rhizobial iron regulator A (RirA) is a global regulator of iron homeostasis in many nitrogen-fixing Rhizobia and related species of α-proteobacteria. It belongs to the widespread Rrf2 super-family of transcriptional regulators and features three conserved Cys residues that characterise the binding of an iron–sulfur cluster in other Rrf2 family regulators. Here we report biophysical studies demonstrating that RirA contains a [4Fe–4S] cluster, and that this form of the protein binds RirA-regulated DNA, consistent with its function as a repressor of expression of many genes involved in iron uptake. Under low iron conditions, [4Fe–4S] RirA undergoes a cluster conversion reaction resulting in a [2Fe–2S] form, which exhibits much lower affinity for DNA. Under prolonged low iron conditions, the [2Fe–2S] cluster degrades to apo-RirA, which does not bind DNA and can no longer function as a repressor of the cell's iron-uptake machinery. [4Fe–4S] RirA was also found to be sensitive to O2, suggesting that both iron and O2 are important signals for iron metabolism. Consistent with this, in vivo data showed that expression of RirA-regulated genes is also affected by O2. These data lead us to propose a novel regulatory model for iron homeostasis, in which RirA senses iron via the incorporation of a fragile iron–sulfur cluster that is sensitive to iron and O2 concentrations.
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DOI：
10.1073/pnas.0500908102
发表时间：
2005-12-20
影响因子：
11.1
作者：
D'Aquino, JA;Tetenbaum-Novatt, J;Ringe, D
通讯作者：
Ringe, D
DOI：
10.1073/pnas.0609514104
发表时间：
2007-02-13
影响因子：
11.1
作者：
Crack, Jason C.;Green, Jeffrey;Thomson, Andrew J.
通讯作者：
Thomson, Andrew J.
影响因子：
4.8
作者：
Agarwalla, S;Stroud, RM;Gaffney, BJ
通讯作者：
Gaffney, BJ
影响因子：
3.6
作者：
Giel JL;Nesbit AD;Mettert EL;Fleischhacker AS;Wanta BT;Kiley PJ
通讯作者：
Kiley PJ
影响因子：
3.6
作者：
Carter, RA;Worsley, PS;Yeoman, KH
通讯作者：
Yeoman, KH