Family matters: Gene regulation by metal-dependent transcription factors

All organisms require trace amounts of metal ions, such as copper, iron, and zinc, since they form an essential component of a number of enzymes. In the past few years many metal-responsive transcriptional regulators have been identified in both prokaryotes and eukaryotes, which can be grouped in distinct families, based on their evolutionary and structural relationships. By regulating systems involved in metal uptake as well as metal efflux and sequestering, these transcription factors help to maintain a delicate balance between necessity and toxicity. Despite the structural similarities within the transcription factor families, individual members can have an affinity for different, and sometimes multiple, metal substrates. The recent availability of crystal structures for key members has led to a detailed understanding of the origins of metal specificity and the mechanisms of transcriptional activation for most of these transcription factor families.