A platform for copper pumps

Abstract

Copper is vital to most cells, but too much is lethal. The structure of a protein that pumps copper ions out of the cytosol provides insight into both the pumping mechanism and how certain mutations in the protein cause disease. See Article p.59 Class IB P-type ATPases perform an important cellular function by regulating the levels of heavy metals, copper in particular, thus providing protein cofactors and maintaining appropriate intracellular concentrations to prevent toxic reactions. In humans, defects in two proteins of this class (the copper pumps ATP7A and ATP7B) give rise to the severe Menkes' and Wilson's diseases. The X-ray crystal structure of a class IB P-type Cu+-ATPase has now been determined in its copper-free state. The structure of CopA from Legionella pneumophila suggests that the copper-transport pathway has three main stages: a cytoplasmic 'entry' site, binding sites in the membrane and an extracellular 'exit' site.