Consequences of manganese replacement of copper for prion protein function and proteinase resistance.
The prion protein (PrP) binds copper and has antioxidant activity enhancing the survival of neurones in culture. The ability of the PrP to bind other cations was tested and it was found that only manganese could substitute for copper. Although initially manganese-loaded PrP exhibited similar structure and activity to copper-loaded PrP, after aging, manganese-loaded PrP became proteinase resistant and lost function. It was also found that manganese could be incorporated into PrP expressed by astrocytes and that this PrP was partially proteinase resistant. These results show that it is possible to generate proteinase-resistant PrP from cells and suggest a possible mechanism for the formation of the scrapie isoform of the PrP as generated in sporadic prion disease.
Brown
D R
DR
Department of Biochemistry, Tennis Court Road, Cambridge University, Cambridge CB2 1QW. drb33@cam.ac.uk
Hafiz
F
F
Glasssmith
L L
LL
Wong
B S
BS
Jones
I M
IM
Clive
C
C
Haswell
S J
SJ
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001667:Binding, Competitive; D001704:Biopolymers / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D002460:Cell Line; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D019286:Endopeptidase K / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D009154:Mutation / Q000235:genetics; D009532:Nickel / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary / Q000187:drug effects; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism
D001704:Biopolymers; D002413:Cations, Divalent; D011328:Prions; D011994:Recombinant Proteins; D008345:Manganese; D003300:Copper; D009532:Nickel; D019286:Endopeptidase K