Metallochaperones

(biochemistry) Metalloproteins that aid in the insertion of the appropriate metal ion into a metalloenzyme. A family of proteins that shuttles metal ions to specific intracellular locations where metalloenzymes bind to the metal ions and use them as cofactors to carry out essential biochemical reactions.

A family of proteins that shuttle metal ions to specific sites within a cell. The target sites for metal delivery include a number of metalloenzymes, or proteins that bind metal ions, such as copper, zinc, or iron, and use these ions as cofactors to carry out essential biochemical reactions. Metallochaperones escort the ion to a specific intracellular location and facilitate incorporation of the metal into designated metalloenzymes. See also Bioinorganic chemistry.

The bulk of current knowledge on metallochaperones is restricted to copper, although it is reasonable to assume that a distinct class of proteins is responsible for the incorporation of other metal ion cofactors into metalloenzymes. Among the metallochaperones that have been studied in detail are a family of three copper chaperones. These molecules operate in eukaryotic (nucleated) cells to direct copper to distinct intracellular locations: the mitochondria, the secretory pathway, and the cytosol. The first copper chaperone identified, COX17, is a small protein that specifically directs copper to the mitochondria. The copper delivered by COX17 is inserted into the metalloenzyme cytochrome oxidase, needed for respiration. A second copper chaperone identified was ATX1, which carries copper to the secretory pathway, a cellular compartment that functions to shuttle proteins toward the cell surface. The metal delivered by ATX1 is incorporated into copper enzymes destined for the cell surface or the extracellular milieu. The most recently identified copper chaperone is CCS, which specifically delivers copper to a single metalloenzyme, superoxide dismutase. This copper-requiring enzyme is located in the soluble cytosolic compartment of the cell and acts to detoxify harmful reactive oxygen species.

Intracellular copper is normally present at exquisitely low levels, and activation of copper enzymes is wholly dependent upon copper chaperones. Copper not only is an essential nutrient but also is quite toxic to living cells, and elaborate detoxification mechanisms prevent the free metal ion from accumulating to any substantial degree. The copper-requiring metalloenzymes cannot compete for these vanishingly low levels of available metal, explaining the requirement for the copper metallochaperones.