Copper chaperone CupA and zinc control CopY regulation of the pneumococcal cop operon

Miranda J. Neubert, Elizabeth A. Dahlmann, Andrew Ambrose, Michael D.L. Johnson

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Any metal in excess can be toxic; therefore, metal homeostasis is critical to bacterial survival. Bacteria have developed specialized metal import and export systems for this purpose. For broadly toxic metals such as copper, bacteria have evolved only export systems. The copper export system (cop operon) usually consists of the operon repressor, the copper chaperone, and the copper exporter. In Streptococcus pneumoniae, the causative agent of pneumonia, otitis media, sepsis, and meningitis, little is known about operon regulation. This is partly due to the S. pneumoniae repressor, CopY, and copper chaperone, CupA, sharing limited homology to proteins of putative related function and confirmed established systems. In this study, we examined CopY metal crosstalk, CopY interactions with CupA, and how CupA can control the oxidation state of copper. We found that CopY bound zinc and increased the DNA-binding affinity of CopY by roughly an order of magnitude over that of the apo form of CopY. Once copper displaced zinc in CopY, resulting in operon activation, CupA chelated copper from CopY. After copper was acquired from CopY or other sources, if needed, CupA facilitated the reduction of Cu2+ to Cu1+, which is the exported copper state. Taken together, these data show novel mechanisms for copper processing in S. pneumoniae.

Original languageEnglish (US)
Article numbere00372-17
Issue number5
StatePublished - Sep 1 2017


  • Chaperones
  • Copper
  • Heavy metals
  • Metal
  • Metal resistance
  • Operon
  • Pneumococcus
  • Repressor
  • Streptococcus pneumoniae
  • Zinc

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


Dive into the research topics of 'Copper chaperone CupA and zinc control CopY regulation of the pneumococcal cop operon'. Together they form a unique fingerprint.

Cite this