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IUBMB Life. 2015 Oct;67(10):737-45. doi: 10.1002/iub.1437. Epub 2015 Sep 30.

Copper-transporting ATPases: The evolutionarily conserved machineries for balancing copper in living systems.

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Department of Plant Molecular Physiology, Institute of Experimental Biology, University of Wroclaw, Wroclaw, Poland.


Copper ATPases (Cu-ATPases) are ubiquitous transmembrane proteins using energy from ATP to transport copper across different biological membranes of prokaryotic and eukaryotic cells. As they belong to the P-ATPase family, Cu-ATPases contain a characteristic catalytic domain with an evolutionarily conserved aspartate residue phosphorylated by ATP to form a phosphoenzyme intermediate, as well as transmembrane helices containing a cation-binding cysteine-proline-cysteine/histidine/serine (CPx) motif for catalytic activation and cation translocation. In addition, most Cu-ATPases possess the N-terminal Cu-binding CxxC motif required for regulation of enzyme activity. In cells, the Cu-ATPases receive copper from soluble chaperones and maintain intracellular copper homeostasis by efflux of copper from the cell or transport of the metal into the intracellular compartments. In addition, copper pumps play an essential role in cuproprotein biosynthesis by the uptake of copper into the cell or delivery of the metal into the chloroplasts and thylakoid lumen or into the lumen of the secretory pathway, where the metal ion is incorporated into copper-dependent enzymes. In the recent years, significant progress has been made toward understanding the function and regulation of Cu-transporting ATPases in archaea, bacteria, yeast, humans, and plants, providing new insights into the specific physiological roles of these essential proteins in various organisms and revealing some conservative regulatory mechanisms of Cu-ATPase activity. In this review, the structural, biochemical, and functional properties of Cu-ATPases from phylogenetically different organisms are summarized and discussed, with particular attention given to the recent insights into the molecular biology of copper pumps in plants.


copper proteins; membrane proteins; organization and expression of plant (nuclear/mitochondrial/chloroplast) genomes; protein function

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