Metalloregulatory proteins Metallothioneins

An intriguing problem about which we know very little is the mechanism of metal identification by the body that triggers Its response, as in the case of the huild-up of metallothioneins upon exposure to toxic metals. Perhaps the best understood of the metalloregulatory proteins is MerR that protects bacteria from mercurial toxicity. It is extremely sensitive to Hg, and distinguishes it from its congeners Zn and Cd. There is good evidence that the mercury receptor forms three-coordinate mercury(II) complexes (see Fig. 12.1c), making possible this specificity. ... 

WJ Cook, SR Kar, KB Taylor, LM Hall. Crystal structure of the cyanobacterial metallothionein repressor SmtB A model for metalloregulatory proteins. J Mol Biol 275 337-346, 1998. 

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).

---