Mode of binding of the Fur protein to target DNA: negative regulation of iron-controlled gene expression

Abstract

Fe2+ binds directly to the Fur protein, which in turn, acquires a configuration capable of binding a specific DNA sequence. Although this chapter deals primarily with negative regulation by iron, it should be noted that several Escherichia coli genes (including acnA, bfr, ftnA, fumA, fumB, sdhCDAB, and sodB) and other bacteria are positively controlled by FeFur. While some of the minor divergences between the different models could be attributed to peculiarities of the Fur proteins from different origins, the ultimate understanding of the Fur-DNA interactions requires accessing the cocrystal of Fur bound to its canonical 19-bp consensus target. Regardless of the specific mechanism by which Fur binds its target DNA, it is possible to describe Fur sites in a genome as an array of the hexamer NAT(A/T)AT. This affords a new interpretation of many previously reported Fur sites. The recent availability of bacterial genomes allows massive comparisons of DNA sequences that can be the target of regulatory proteins. In particular, some Fur-binding sites and some UP elements seem to occasionally coincide in the chromosome of E. coli.