In some species the arrangement of these genes in the genome is different than in Escherichia coli [5]. KdpD exhibits both kinase and phosphatase activities towards KdpE [10, 11, 12]. Under K⁺-limiting conditions or under osmotic stress imposed by a salt, autophosphorylation of KdpD at His-673 is stimulated [5, 13, 14]. Subsequently, the phosphate group is transferred from KdpD to Asp-52 of KdpE [10, 15, 16], leading to the dimerization and activation of KdpE [17]. Two domains of KdpE, the receiver and the DNA-binding domains, interact with KdpD for efficient signal transduction [18]. At high concentrations of K⁺, the kinase activity of KdpD is inhibited [13]. Under salt stress, the universal stress protein UspC binds to KdpD and stabilizes the KdpD-KdpE-DNA complex; therefore, this system can be activated even though K⁺ accumulates under this environmental condition [19]. In addition, expression of the kdpFABC operon is regulated by the phosphoryl group transfer chain Ntr-PTS: dephosphorylated enzyme IIA^Ntr binds to KdpD, and this interaction strongly stimulates KdpD kinase activity [20]. KdpE is a member of the OmpR/PhoB subfamily of response regulators [8, 21] and binds a 23-bp recognition sequence [3]. The crystal structure of KdpE with and without bound beryllium fluoride has been solved [17]. KdpE is not an essential protein [22]. Overproduction of KdpE causes a drug resistance phenotype [23]. The crystal structure at 3Å resolution of KdpE bound to the catalytic domain of KdpD was reported [18].