Roles of transition metals in signal transduction and gene expression

Transition metals are essential nutrients and cofactors but can also play important roles in signaling processes. To gain insights into the biological chemistry of the transition metals we are studying the receptors known as metalloregulatory proteins. These metal-activated proteins play a central role in the cell biology of the transition metals and exert metal-responsive control of genes involved in respiration, metabolism or in metal-specific homeostasis. Evaluation of stress-responsive regulation in the microbial iron-uptake and storage systems (Fur, DtxR), copper-efflux (PcoR/PcoS) and mercury-detoxification (MerR) is underway. Two allosteric mechanisms for control of gene expression was first discovered in metalloregulatory systems including a mercury-responsive DNA-distortion mechanism for transcriptional control of detoxification genes by MerR. The ultrasensitive switching mechanism gives rise in this case to a rapid physiological response as Hg(II) exceeds a dangerous threshold. Recent advances in regulation of intracellular zinc and copper concentrations focus on the inorganic chemistry of receptors involved in metal ion transport storage and utilization. The chemistry to be discussed concerns transition meta! homeostasis and may be useful in understanding fatal metal based disorders in humans, including Menke's and Wilson's diseases.