PrPSc-like prion protein peptide inhibits the function of cellular prion protein.
Mice lacking expression of the prion protein are protected against infection with prion disease. Neurodegeneration in prion disease requires the formation of the abnormal isoform of the prion protein (PrP(Sc)) from host prion protein. Therefore expression of normal host prion protein is necessary for prion disease. In the present investigation, it was demonstrated that PrP(Sc) and a peptide resembling PrP(Sc), PrP106-126, both bind to cellular prion protein at amino acid residues 112-119. Interaction between PrP106-126 and the prion protein strips the prion protein from cells. Direct interaction of PrP106-126 with the prion protein was found to make cells more susceptible to copper toxicity, inhibited copper uptake into cells and inhibited the superoxide dismutase-like activity of the prion protein. Direct inhibition of prion protein function by PrP(Sc) may be necessary for neurodegeneration in prion disease.
Brown
D R
DR
Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, U.K. drb33@cam.ac.uk
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D051379:Mice; D016296:Mutagenesis; D010446:Peptide Fragments / Q000494:pharmacology*; D018620:PrPSc Proteins / Q000737:chemistry*; D011328:Prions / Q000037:antagonists & inhibitors* / Q000235:genetics
D017931:DNA Primers; D010446:Peptide Fragments; D018620:PrPSc Proteins; D011328:Prions