Copper and the prion protein: methods, structures, function, and disease.
The transmissible spongiform encephalopathies (TSEs) arise from conversion of the membrane-bound prion protein from PrP(C) to PrP(Sc). Examples of the TSEs include mad cow disease, chronic wasting disease in deer and elk, scrapie in goats and sheep, and kuru and Creutzfeldt-Jakob disease in humans. Although the precise function of PrP(C) in healthy tissues is not known, recent research demonstrates that it binds Cu(II) in an unusual and highly conserved region of the protein termed the octarepeat domain. This review describes recent connections between copper and PrP(C), with an emphasis on the electron paramagnetic resonance elucidation of the specific copper-binding sites, insights into PrP(C) function, and emerging connections between copper and prion disease.
Millhauser
Glenn L
GL
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA. glennm@chemistry.ucsc.edu
D000818:Animals; D003300:Copper / Q000737:chemistry* / Q000378:metabolism*; D004194:Disease; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D006801:Humans; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation
D011328:Prions; D003300:Copper