The Schizosaccharomyces pombe Pccs protein functions in both copper trafficking and metal detoxification pathways

Julie Laliberté, Lisa J. Whitson, Jude Beaudoin, Stephen P. Holloway, P. John Hart, Simon Labbé

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25 Scopus citations

Abstract

Because copper is both an essential cofactor and a toxic metal, different strategies have evolved to appropriately regulate its homeostasis as a function of changing environmental copper levels. In this report, we describe a metallochaperone-like protein from Schizosaccharomyces pombe that maintains the delicate balance between essentiality and toxicity. This protein, designated Pccs, has four distinct domains. SOD activity assays reveal that the first three domains of Pccs are necessary and sufficient to deliver copper to its target, copper-zinc superoxide dismutase (SOD1). Pccs domain IV, which is absent in Saccharomyces cerevisiae CCSI, contains seventeen cysteine residues, eight pairs of which are in a potential metal coordination arrangement, Cys-Cys. We show that S. cerevisiae ace1Δ mutant cells expressing the full-length Pccs molecule are resistant to copper toxicity. Furthermore, we demonstrate that the Pccs domain IV enhances copper resistance of the ace1Δ cells by an order of magnitude compared with that observed in the same strain expressing a pccs+I-II-III allele encoding Pccs domains I-III. We consistently found that S. pombe cells disrupted in the pccs+ gene exhibit an increased sensitivity to copper and cadmium. Furthermore, we demonstrate that overexpression of pccs+ is associated with increased copper resistance in fission yeast cells. Taken together, our findings suggest that Pccs activates apo-SOD1 under copper-limiting conditions through the use of its first three domains and protects cells against metal ion toxicity via its fourth domain.

Original languageEnglish (US)
Pages (from-to)28744-28755
Number of pages12
JournalJournal of Biological Chemistry
Volume279
Issue number27
DOIs
StatePublished - Jul 2 2004

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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