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- Title
The cellular prion protein binds copper in vivo.
- Authors
Brown, D R; Qin, K; Herms, J W; Madlung, A; Manson, J; Strome, R; Fraser, P E; Kruck, T; von Bohlen, A; Schulz-Schaeffer, W; Giese, A; Westaway, D; Kretzschmar, H
- Abstract
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.
- Publication
Nature, 1997, Vol 390, Issue 6661, p684
- ISSN
0028-0836
- Publication type
Journal Article
- DOI
10.1038/37783