Iron regulation

D. Hide, M. Broderius, J. Fett, and M. L. Guerinot, A novel iron-regulated metal transporter from plants identified by functional expression in yeast. Proc. Natl. Acad. Sci. U.S.A. 93 5624 (1996). 

Recent studies have further examined the iron stress response of pseudomonads using an iron-regulated, ice-nucleation gene reporter (inaZ) for induction of the iron stress response (17,18,84). This particular reporter system was developed by Loper and Lindow (85) for study of microbial iron stress on plant surfaces but was later employed in soil assays. In initial. studies, cells of Pseudomonas fluorescens and P. syringae that contained the pvd-inaZ fusion were shown to express iron-responsive ice-nucleation activity in the bean rhizosphere and phyllosphere. Addition of iron to leaves or soil reduced the apparent transcription of the pvd-inaZ reporter gene, as shown by a reduction in the number of ice nuclei produced. 

The Fur protein from E. coli was isolated in one step due to its high affinity for metal-chelate columns loaded with zinc. In DNase footprinting experiments, the Fur protein was shown to bind DNA in the promoter region of several iron-regulated genes. The consensus sequence, called the Fur box, is GATAATGATAATCATT ATC. In vitro binding is dependent on the divalent cations Co2+ Mn2+ /s Cd2+ Cu2+ at 150 iM, while Fe2+ seemed to be less active at this concentration, probably due to oxidation to Fe3+ (De Lorenzo et al., 1987). The unspecificity for divalent metals observed in vitro shows that the cells have to select the ions transported carefully and have to balance their active concentrations. In addition, it is a caveat for the experimenter to test a hypothesis on metal-ion specificity not only in vitro, but also in vivo. 

Genes regulated by Fur code for proteins that function in iron transport and iron metabolism under aerobic conditions, iron metabolism is associated with oxidative stress. In addition, some virulence factors are regulated by Fur. Table 3.2 lists examples and functions of Fur- and iron-regulated genes in E. coli, including pathogenic E. coli strains. 

Mazmanian, S. K., Ton-That, H., Su, K. and Schneewind, O. (2002). An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis, Proc. Natl Acad. Sci. USA, 99, 2293-2298. 

Crosa, J. H. (1997). Signal transduction and transcriptional and post transcriptional control of iron-regulated genes in bacteria, Microbiol. Mol. Biol. Rev., 61, 319-336. 

Fur is itself part of the family of gene regulatory proteins throughout many bacterial species. The major subclass is mainly involved, like Fur in E. coli, in the control of iron homeostasis, but it can also function in acid tolerance and protection against oxidative stress. Fur also controls the iron-regulated expression of bacterial virulence determinants. One class of the Fur family, Zur, is involved in the regulation of zinc uptake (see below). 

Alterations in brain iron metabolism have been reported, resulting in increased iron accumulation in Huntington s disease. This was particularly the case in basal ganglia from patients with HD compared to normal controls. In studies in embryonic stem cells, huntingtin was found to be iron-regulated, essential for the function of normal nuclear and perinuclear organelles and to be involved in the regulation of iron homeostasis. 

Figure 15.19 Regulation of the aconitase/iron-regulating protein balance. A low iron concentration increases the amount of the iron-regulating protein, the role of which is to regulate the iron concentration in the cell. A high iron concentration lowers the amount of the iron-regulating protein and increases that of aconitase.

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