The cellular prion protein binds copper in vivo

D R Brown, K Qin, J W Herms, A Madlung, J Manson, R Strome, P E Fraser, T Kruck, A von Bohlen, W Schulz-Schaeffer, A Giese, D Westaway, H Kretzschmar

Research output: Contribution to journalArticlepeer-review


The normal cellular form of prion protein (PrPC) is a precursor to the pathogenic protease-resistant forms (PrPSc) believed to cause scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease. Its amino terminus contains the octapeptide PHGGGWGQ, which is repeated four times and is among the best-preserved regions of mammalian PrPC. Here we show that the amino-terminal domain of PrPC exhibits five to six sites that bind copper (Cu(II)) presented as a glycine chelate. At neutral pH, binding occurs with positive cooperativity, with binding affinity compatible with estimates for extracellular, labile copper. Two lines of independently derived PrPC gene-ablated (Prnp0/0) mice exhibit severe reductions in the copper content of membrane-enriched brain extracts and similar reductions in synaptosomal and endosome-enriched subcellular fractions. Prnp0/0 mice also have altered cellular phenotypes, including a reduction in the activity of copper/zinc superoxide dismutase and altered electrophysiological responses in the presence of excess copper. These findings indicate that PrPC can exist in a Cu-metalloprotein form in vivo.

Original languageEnglish
Pages (from-to)684-7
Number of pages4
Issue number6661
Publication statusPublished - 31 Dec 1997


  • Animals
  • Brain
  • Cells, Cultured
  • Cerebellum
  • Copper
  • Electrophysiology
  • Humans
  • In Vitro Techniques
  • Kidney
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • Muscles
  • PrPC Proteins
  • Protein Binding
  • Purkinje Cells
  • Synapses


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