Sensing Metals - the Versatility of Fur

Abstract

Metals are essential for cell growth and survival as cofactors of diverse enzymes and as structural and regulatory ligands for various cell components. In excess amount, however, even essential metals become toxic to cells. In order to maintain proper levels of the metals inside the cell, sensors detect the availability of specific metals inside and around the cell, and regulate target genes that encode proteins responsible for acquisition, mobilization, usage, storage, and export of the corresponding metals. Among metal-sensing transcriptional regulators that modulate their activity through binding metals, Fur family regulators show remarkable diversity in the types of metals they respond and the breadth of target genes they regulate. Since the discovery of Fur as an iron-dependent inhibitor of iron uptake system in Escherichia coli and Salmonella in the late 70’s, the prototypical role of Fur as a transcriptional repressor in the presence of iron has been firmly established in a wide range of bacteria. However, in the last 10 years, we have witnessed an explosion of discoveries of diverse Fur subfamilies that are specialized to sense metals other than iron, such as zinc (Zur), manganese (Mur), heme iron (Irr), and nickel (Nur), to control homeostasis of each specific metal. A subfamily (PerR) that is specialized to sense peroxide through bound iron and control genes for oxidative s