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

Pellicer Martinez, Ma Teresa and Martinez, Ana Bermejo and Crack, Jason C and Holmes, John D and Svistunenko, Dimitri A and Johnston, Andrew WB and Cheesman, Myles R and Todd, Jonathan D and Le Brun, Nick E (2017) 'Sensing iron availability via the fragile [4Fe–4S] cluster of the bacterial transcriptional repressor RirA.' Chemical Science, 8 (12). 8451 - 8463. ISSN 2041-6539

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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.

Item Type: Article
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Elements
Date Deposited: 18 Sep 2018 11:11
Last Modified: 06 Sep 2019 14:15
URI: http://repository.essex.ac.uk/id/eprint/23045

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