Primary structure of two P-type ATPases involved in copper homeostasis in Enterococcus hirae.
We cloned an operon, copAB, from Enterococcus hirae encoding two P-type ATPases of 727 and 745 amino acids, respectively. Both enzymes display heavy metal ion binding motifs in their polar N-terminal region. With an antibody against CopB, we showed on Western blots that expression of the operon is induced by either low or high ambient copper concentrations. Disruption of the copA gene renders the cells dependent, whereas copper disruption of copB results in a copper-sensitive phenotype. CopA exhibits 35% sequence similarity to CopB and 43% similarity to the ATPase encoded by the recently cloned human Mc1 gene, a gene responsible for the Menkes inborn error of copper metabolism. Our results imply that CopA and CopB are heavy metal ion ATPases that regulate the cytoplasmic copper activity, with CopA serving in the uptake and CopB in the extrusion of copper.
Odermatt
A
A
Department of Clinical Pharmacology, University of Berne, Switzerland.
Suter
H
H
Krapf
R
R
Solioz
M
M
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000201:enzymology; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D019327:Copper Sulfate; D000079922:Copper Transport Proteins; D000073840:Copper-Transporting ATPases; D004269:DNA, Bacterial / Q000235:genetics; D016983:Enterococcus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D005798:Genes, Bacterial; D006706:Homeostasis; D008670:Metals / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009876:Operon; D010641:Phenotype; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D012835:Silver Nitrate / Q000494:pharmacology
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D004269:DNA, Bacterial; D008670:Metals; D003300:Copper; D012835:Silver Nitrate; D000251:Adenosine Triphosphatases; C088359:CopB ATPase, Enterococcus hirae; D000073840:Copper-Transporting ATPases; D019327:Copper Sulfate