Ferric uptake regulator

TF transcription factor, R receptor, Fur ferric uptake regulation protein, NF-kB nuclear factor-kB, AP-1 activator protein-1, Egr-1 early growth response-1, VDR la,25-dihydroxy-vitamin D3 receptor, RXR retinoid X receptor, PPARy peroxisome proliferator-activated receptor y NFAT nuclear factor of activated T-cells, HSF heat shock factor, p53 tumor suppressor p53, HIF-1 hypoxia inducible factor-1. ... 

Pohl, E., Haller, J.C., Mijovilovich, A., Meyer-Klauke, W., Garman, E. and Vasil, M.L. (2003) Architecture of a protein central to iron homeostasis crystal structure and spectroscopic analysis of the ferric uptake regulator, Molec. Microbiol., 47, 903-915. 

Once the siderophore-iron complexes are inside the bacteria, the iron is released and utilized for vital cell functions. The iron-free hydroxamate siderophores are commonly re-excreted to bring in an additional iron load (Enterobactin is at least partially degraded by a cytoplasmic esterase This cycle is repeated until specific intracellular ferric uptake regulation proteins (Fur proteins) bind iron, and signal that the intracellular iron level is satisfactory, at -which point ne-w siderophore and siderophore-receptor biosynthesis are halted and the iron-uptake process stops. This intricate feedback mechanism allows a meticulous control over iron(III) uptake and accumulation against an unfavorable concentration gradient so as to maintain the intracellular iron(III) level within the required narrow window. Several excellent reviews concerning siderophore-iron transport mechanisms have been recently published i.3,i6, is,40,45,60-62 ... 

As is pointed out in Chapter 16, the acquisition of iron and control of its concentration is of crucial importance to bacteria. In E. coli the Fe2+-binding protein Fur (ferric uptake regulator) represses promoters controlling siderophore biosynthesis as well as other responses. It is a global regulator that controls 40 transcriptional units.124 Similar proteins repress synthesis of the diphtheria toxin by Corynebac-terium diphtheriae,125 126 uptake of iron in these bacteria and in Mycobacterium tuberculosis,127 and uptake of molybdate.1273... 

The iron acquisition systems of E. coli and many other bacteria are regulated at the level of RNA transcription by Fur (ferric uptake regulator), a transcriptional repressor that exhibits ferrous iron-dependent, DNA-binding activity. Fur is expressed as a 17 kDa homodimer and, under conditions of iron sufficiency, it binds one iron ion per subunit, which increases its affinity for its preferred DNA binding sites by 1000-fold. ... 

The Fur (Ferric uptake regulation) protein is a negative regulator of the aerobactin-operon and of several other siderophore-mediated, high affinity iron transport systems in... 

Bereswill, S., Greiner, S., van Vliet, A. H., Waidner, B., Fassbinder, F., Schiltz, E., Kusters, J. G. and Kist, M. 2000, Regulation of ferritin-mediated c)4oplasmic iron storage by the ferric uptake regulator homolog (Fur) of Helicobacter pylori. J.Bacteriol., 182 5948-5953... 

Mills SA, Marietta MA. 2005. Metal binding characteristics and role of iron oxidation in the ferric uptake regulator from icAerfc/ /a coli. Biochemistry 44(41) 13553-13559. 

A different strategy was used to characterize the structure of the ferric-uptake regulation factor Fur [174]. As a first approach, the reactivity (accessibility) of each lysine residue was investigated by chemical modification followed by ESI MS. After metal activation, K76 was found to be protected from the modification reaction in the presence of DNA. The conformational... 

Gonzalez de Peredo, A. Saint-Pierre, C. Latour, J. M. Michaud-Soret, 1. Forest, E. Conformational changes of the ferric uptake regulation protein upon metal activation and DNA binding First evidence of structural homologies with the diphtheria toxin repressor. J. Mol Biol 2001, 3/0(1), 83-91. 

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