title: The Enterococcus hirae paradigm of copper homeostasis: copper chaperone turnover, interactions, and transactions.
abstract: The cop operon is a key element of copper homeostasis in Enterococcus hirae. It encodes two copper ATPases, CopA and CopB, the CopY repressor, and the CopZ metallochaperone. The cop operon is induced by copper, which allows uncompromised growth in up to 5 mM ambient copper. Copper uptake appears to be accomplished by the CopA ATPase, a member of the heavy metal CPx-type ATPases and closely related to the human Menkes and Wilson ATPases. The related CopB ATPase extrudes copper when it reaches toxic levels. Intracellular copper routing is accomplished by the CopZ copper chaperone. Using surface plasmon resonance analysis, it was demonstrated that CopZ interacts with the CopA ATPase where it probably becomes copper loaded. CopZ in turn can donate copper to the copper responsive repressor CopY, thereby releasing it from DNA. In high copper, CopZ is proteolyzed. Cell extracts were found to contain a copper activated proteolytic activity that degrades CopZ in vitro. This post-translational control of CopZ expression presumably serves to avoid the accumulation of detrimental Cu-CopZ levels.
authors.affiliation: Dept. of Clinical Pharmacology, University of Berne, 3010 Berne, Switzerland.
authors.forename: Zen Huat
authors.initials: ZH
authors.lastname: Lu
authors.forename: Charles T
authors.initials: CT
authors.lastname: Dameron
authors.forename: Marc
authors.initials: M
authors.lastname: Solioz
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D016983:Enterococcus / Q000235:genetics* / Q000378:metabolism*; D006706:Homeostasis; D008954:Models, Biological; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D012097:Repressor Proteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; C092378:CopY protein, Enterococcus hirae; C092379:CopZ protein, Enterococcus hirae; D018832:Molecular Chaperones; D012097:Repressor Proteins; D015534:Trans-Activators; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases