The Global Transcription Factor Fur Is Activated by Binding a [2Fe-2S] Cluster to Maintain Iron Homeostasis in Escherichia coli
Doctor of Philosophy (PhD)
Iron is an essential element for biological functions. Organisms have developed specific mechanisms to acquire, store, and export iron to manage intracellular iron homeostasis. These mechanisms are crucial not only for providing the cells with adequate iron for biological processes but also for ensuring that cells are not overloaded with excess iron, which is highly toxic. The Ferric uptake regulator (Fur) is a global transcription factor for maintaining intracellular iron homeostasis in bacteria. Previously, it was postulated that when the intracellular iron content is elevated, Fur binds ferrous iron to down-regulate the iron acquisition genes and up- regulate the iron storage genes. Nevertheless, the iron-bound Fur has never been identified. My research has demonstrated that Escherichia coli Fur binds a [2Fe-2S] cluster, not mononuclear iron, when intracellular iron content is elevated and that the binding of the [2Fe-2S] cluster in Fur is coordinated by the conserved cysteine residues in the C-terminal domain. Furthermore, the binding of a [2Fe-2S] cluster in Fur is highly conserved among Fur homologs. Utilizing the specific Fur binding sequence known as Fur-box as a DNA binding probe, we have also found that binding of a [2Fe-2S] cluster in Fur turns on its Fur-box binding activity as an active repressor. Based on these findings, we propose a new model that when intracellular iron content is elevated, Fur binds a [2Fe-2S] cluster to regulate intracellular iron homeostasis in bacteria.
Fontenot, Chelsey Rene, "The Global Transcription Factor Fur Is Activated by Binding a [2Fe-2S] Cluster to Maintain Iron Homeostasis in Escherichia coli" (2023). LSU Doctoral Dissertations. 6131.
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