Proteins That Can Spare a Few Coppers

The self-starters of the cell, enzymes kick a host of crucial reactions into action. Now it turns out that some of them need a little help to get going. In this week’s Science, scientists report that an enzyme responsible for sopping up dangerous free radicals won’t work until small proteins deliver its catalytic copper ion. Researchers hope the insight will lead to new research on Lou Gehrig’s disease, where a malfunctioning copper-bearing enzyme is to blame.

Just as a car needs platinum in its catalytic converter, many enzymes–biological catalysts–need metal ions such as copper. Until recently, researchers assumed these proteins simply grabbed free-roaming metal ions. In 1997, however, geneticist Valeria Culotta of Johns Hopkins University in Baltimore and chemist Thomas O’Halloran of Northwestern University in Evanston, Illinois, discovered that a protein hand delivers copper to an enzyme.

To determine whether this sort of helper protein was absolutely necessary, the team has now examined another copper-containing enzyme called superoxide dismutase. In yeast that lacked the gene for a “copper chaperone,” which the researchers named CCS, superoxide dismutase was kaput, unable to sop up radicals. The enzyme only perked up when they increased the concentration of copper a hundredfold. A normal cell, they calculated, never contains copper ions floating in the cytoplasm. Any loose copper is probably tied up by other molecules. “That’s why you need metallochaperones,” O’Halloran says. “Without them, the target proteins will not get their metals.”

It’s likely that other biologically important metals have metallochaperones as well, according to Dennis Winge, a biochemist at the University of Utah in Salt Lake City. “This work in yeast is catalyzing a new field” of metal trafficking in cells, he says. What’s more, the research could lead to a better understanding of Lou Gehrig’s disease, in which mutated superoxide dismutase damage motor neurons. Researchers think that without copper, the enzyme might not wreak such havoc. If so, blocking CCS may be a way to treat the disease.

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