Metalloregulatory transcription

Fig. 1. Schematic overview of copper trafficking and homeostasis inside the yeast cell. The actions of Mad and Ace 1, copper-dependent metalloregulatory transcription factors, control the production of copper import [copper transporter (Ctr) and reductase (Fre)] and detoxification/sequestration [metallothionein (MT)] machineries, respectively. Three chaperone-mediated delivery pathways are shown. Atxl shuttles Cu(I) to the secretory pathway P-type ATPase Ccc2 (right). CCS delivers Cu(I) to the cytoplasmic enzyme copper-zinc superoxide dismutase (SOD) (left). Coxl7 shuttles Cu(I) to cytochrome c oxidase (CCO) in the mitochondria (bottom). Mitochondrial proteins Scol and Sco2 may also play a role in copper delivery to the CuA and CuB sites of CCO. Copper metabolism and iron metabolism are linked through the actions of Fet3, a copper-containing ferroxidase required to bring iron into the cell (lower right) (see text).

Busenlehner LS, Pennella MA, Giedroc DP. The SmtB/ArsR family of metalloregulatory transcriptional repressors structural insights into prokaryotic metal resistance. FEMS Microbiol. Rev. 2003 27 131-143. 

One of the first metalloregulatory proteins to be characterized extensively is the prokaryotic MerR transcription factor (1, 6, 7), which acts either as a repressor (apo-protein) or an activator (holo-protein) of the mer operon encoding mercury resistance proteins (Fig. Ic). The —35 and —10 sequence elements of the mer promoter, binding sites for the RNA polymerase initiation complex, are separated by an unusually long distance that results in poor constitutive transcription. Apo-MerR binds to the DNA between these sequences and bends the DNA, which results in a slight increase in repression on the suboptimal promoter. It also recruits the RNA polymerase to the transcription start site where it waits in a stalled complex. Upon binding of... 

Bittel, D.C., I.V. Smirnova and G.K. Andrews. Functional heterogeneity in the zinc fingers of metalloregulatory protein metal response element-binding transcription factor-1. J. Biol. Chem. 275 37194-37201, 2000. 

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