Crystal structure of a copper-transporting PIB-type ATPase

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.