Coordinating intracellular nickel-metal-site structure-function relationships and the NikR and RcnR repressors

Metalloregulator function requires both sensitivity and selectivity to ensure metal-specific activity without interfering with intracellular metal trafficking pathways. Here, we examine the role of metal-coordination geometry in the function of NikR and RcnR, two widely conserved nickel-responsive regulators that are both present in E. coli. The available data suggest an emerging trend in which coordination number is linked to metal-binding affinity, and thus regulatory function. The differences in coordination geometry also suggest that the kinetic mechanisms of metal-association and dissociation will contribute to metalloregulator function. We also discuss ways in which the ligand-binding properties of metalloregulators may be tuned to alter the regulatory response.