Chemists characterize regulators of zinc intake and export in cells

EVANSTON, Ill. Chemists at Northwestern University have acquired new insight into how zinc pumps and their regulatory proteins function in cells. The findings, to be published online June 8 in the journal Science, should improve our knowledge of diseases related to zinc metabolism as well as influence future drug design and pharmaceuticals.

Inorganic elements, such as zinc, copper and iron, are vital to the healthy functioning of cells in living organisms, but little is known about how cells use these heavy metals. Each cell in the human body, for instance, requires an enormous amount of zinc, but that amount must be carefully controlled because zinc can be destructive in excess. How does the cell monitor the amount of zinc inside its walls?

Thomas V. OHalloran, professor of chemistry, and Caryn Outten, a former Ph.D. student of OHallorans, have solved an important part of the puzzle. They have described the mechanisms by which two sensor proteins regulate two pumps embedded in the cell membrane. One pump draws zinc into the cell when it is needed, and the other acts as a bouncer, ejecting zinc when the cell is saturated. These are the first and appear to be the primary zinc pumps, along with their regulatory proteins, identified in a cell.

The researchers also have shown that, contrary to current thinking, cells have no free-floating zinc; instead, all zinc is accounted for when in the cell, either bound to proteins or acting as a catalyst in biochemical reactions. This suggests the existence of zinc "chaperone" proteins whose role would be to escort the metal safely to the specific site where it is needed.

"Our work with zinc, copper and other metals involved in human health and disease is helping us to better understand the role these metals play in our body," said OHalloran, who discovered the first copper chaperone protein in 1997.

OHalloran and Outten studied the zinc regulatory proteins in the bacteria E. coli, wh

Contact: Megan Fellman
Northwestern University

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