Cop operon

In microbes without a permeability barrier, or when the barrier fails, a mechanism must be in place to export metals from the cytoplasm. These active transport systems involve energy-dependent, membrane-bound efflux pumps that can be encoded by either chromosomal- or plasmid-borne genes. Active transport is the most well-studied metal resistance mechanism. Some of these include the ars operon for exporting arsenic from E. coli, the cad system for exporting cadmium from Staphylococcus aureus, and the cop operon for removing excess copper from Enterococcus hiraeP i9A0... 

Figure 12.2 Copper chaperone function, (a) Copper homeostasis in Enterococcus hirae is affected by the proteins encoded by the cop operon. CopA, Cu1+-import ATPase CopB, Cu1+-export ATPase CopY, Cu1+-responsive repressor copZ, chaperone for Cu1+ delivery to CopY. (b) The CTR family of proteins transports copper into yeast cells. Atxlp delivers copper to the CPx-type ATPases located in the post Golgi apparatus for the maturation of Fet3p. (c) Coxl7p delivers copper to the mitochondrial intermembrane space for incorporation into cytochrome c oxidase (CCO). (d) hCTR, a human homologue of CTR, mediates copper-ion uptake into human cells. CCS delivers copper to cytoplasmic Cu/Zn superoxide dismutase (SOD1). Abbreviations IMM, inner mitochondrial membrane OMM, outer mitochondrial membrane PM, plasma membrane PGV, post Golgi vessel. Reprinted from Harrison et al., 2000. Copyright (2000), with permission from Elsevier Science.

Because of their importance in many enzymes, bacteria have had to develop uptake systems for copper and zinc. Copper uptake (and homeostasis, which is discussed in Chapter 8) has been extensively studied in the Gram-positive bacterium Enterococcus hirae. Two of the genes in the cop operon, copA and copB, encode membrane ATPases. An extracellular reductase CorA reduces Cu2+ to Cu+, which is taken up by CopA when copper is limiting. 

Magnani, D. and Solioz, M. (2005) Copper chaperone cycling and degradation in the regulation of the cop operon of Enterococcus hirae, BioMetals, 18, 407-412. 

Fig. 5. Copper homeostasis in Enterococcus hirae. Under copper-limiting conditions, copper is pumped into the cell by CopA. The CopZ copper chaperone picks up copper at this site of entry. Under physiological copper conditions, Zn(II)CopY binds to the promoter and represses transcription of the cop operon. Under conditions of copper excess, Cu-CopZ donates Cu(I) to CopY, which leads to the replacement of the Zn(II), loss of DNA-binding affinity, and ultimately synthesis of the operon products. Excess copper is secreted by the CopB efflux pump. The substrate for this pump may be a copper-glutathione (GSH) complex, rather than Cu-CopZ.

Fig. 6. Occurrence of the CXCX(4 5) CXC consensus motif. CopY, cop operon repressor protein from Enterococcus hirae Mad, transcription factor for the Ctrl copper transporter of Saccharomyces cerevisiae AMTl, transcription factor for metal-lothionein from Candida albicans ACEl, transcription factor for metallothionein from Sa. cerevisiae Grisea, MACl orthologue of Podospora anserina MT-2 p-domain, N-terminal domain of human metallothionein-2.

In the gram-positive bacteria Enterococcus hirae, copper homeostasis is maintained by the cop operon, consisting of the copA, copB, copY, and copZ... 

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