The cellular prion protein binds copper in vivo

@article{Brown1997TheCP,
  title={The cellular prion protein binds copper in vivo},
  author={David R Brown and Kefeng Qin and Jochen Herms and Axel Madlung and Jean C Manson and Robert R Strome and Paul E. Fraser and Theo P. A. Kruck and Alex von Bohlen and Walter J. Schulz-Schaeffer and Armin Giese and David Westaway and Hans A. Kretzschmar},
  journal={Nature},
  year={1997},
  volume={390},
  pages={684-687}
}
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 PrPCexhibits five to six sites that bind copper (Cu(II)) presented as a glycine chelate. At… Expand
Copper Converts the Cellular Prion Protein into a Protease-resistant Species That Is Distinct from the Scrapie Isoform*
TLDR
It is demonstrated using a conformation-dependent immunoassay that copper-treated PrP is structurally distinct from PrPSc, consistent with the idea that the metal alters the biochemical properties of PrP by directly binding to this region. Expand
Mouse brain synaptosomes accumulate copper-67 efficiently by two distinct processes independent of cellular prion protein
TLDR
The results demonstrate that mouse brain synaptosomes accumulate copper efficiently by at least two distinct mechanisms, and indicate thatsynaptosomal copper uptake is independent of PrPC. Expand
Copper(II) Binding to the Human Doppel Protein May Mark Its Functional Diversity from the Prion Protein*
TLDR
It is shown that in vitro binding of copper(II) to human recombinant Dpl occurs with a different pattern from that observed for recombinant PrP, suggesting that binding of the ion to PrPC and Dpl may contribute to the different functional roles ascribed to these highly homologous proteins. Expand
Biology of the prion gene complex.
TLDR
The interaction between the Prnp and Prnd genes in mouse cerebellar neurons may have a physical correlate in competition between Dpl and PrPC within a common biochemical pathway that, when misregulated, leads to apoptosis. Expand
Effect of copper and manganese on the de novo generation of protease-resistant prion protein in yeast cells.
TLDR
This study demonstrates the involvement of PrP in the regulation of intracellular metal ion homeostasis and uncovers copper and manganese ions as in vivo risk factors for the conversion into PrP(Sc). Expand
The functional links between prion protein and copper.
TLDR
Evidence relates PrPC to copper metabolism and oxidative stress as suggested by its copper-binding properties in the N-terminal octapeptide repeat region, and in vivo experiments suggesting the physiological relevance of PrPC interaction with heparan sulfate proteoglycans are discussed. Expand
Copper binding is the governing determinant of prion protein turnover
TLDR
It is shown that physiological levels of Cu promote internalisation of PrP(c), a copper (Cu) binding glycoprotein with a rapid basal turnover, and the decrease in detectable levels at the cell surface following Cu treatment was the result of rapid internalisation rather than loss into the surrounding environment. Expand
Aberrant metal binding by prion protein in human prion disease
TLDR
The results suggest that altered metal‐ion occupancy of PrP plays a pivotal role in the pathogenesis of prion diseases and presented two potential approaches in the diagnosis of CJD; the significant increase in brain manganese makes it potentially detectable by MRI, and the binding ofManganese by PrP in sCJD might represent a novel diagnostic marker. Expand
Prion protein fate governed by metal binding.
TLDR
The use of near-infrared spectroscopy for studies on aqueous solutions of prion protein binding Cu or Mn indicates that PrP binds both Mn and Cu differently, andalyses of Cu binding suggest that the PrP-Cu complex protected Cu from the water increasing protein stability. Expand
Expression of Prion Protein Increases Cellular Copper Binding and Antioxidant Enzyme Activities but Not Copper Delivery*
TLDR
The N-terminal region of the prion protein PrPC contains a series of octapeptide repeats that are implicated in the binding of divalent metal ions, particularly copper and a link between PrPC, copper binding, and resistance to oxidative stress is reported. Expand
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