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Issue 12, 2017
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Sensing iron availability via the fragile [4Fe–4S] cluster of the bacterial transcriptional repressor RirA

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Abstract

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.

Graphical abstract: Sensing iron availability via the fragile [4Fe–4S] cluster of the bacterial transcriptional repressor RirA

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Publication details

The article was received on 23 Jun 2017, accepted on 20 Oct 2017 and first published on 23 Oct 2017


Article type: Edge Article
DOI: 10.1039/C7SC02801F
Citation: Chem. Sci., 2017,8, 8451-8463
  • Open access: Creative Commons BY license
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    Sensing iron availability via the fragile [4Fe–4S] cluster of the bacterial transcriptional repressor RirA

    M. T. Pellicer Martinez, A. B. Martinez, J. C. Crack, J. D. Holmes, D. A. Svistunenko, A. W. B. Johnston, M. R. Cheesman, J. D. Todd and N. E. Le Brun, Chem. Sci., 2017, 8, 8451
    DOI: 10.1039/C7SC02801F

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