Copper has differential effect on prion protein with polymorphism of position 129.
The pathology of human prion diseases is affected by polymorphism at amino acid residue 129 of the prion protein gene. Recombinant mouse prion proteins mimicking either form of the polymorphism were prepared to examine their effect on the conformation and the level of superoxide dismutase (SOD) activity of the prion protein. Following the binding of copper atoms to prion protein, antibody mapping and CD analysis detected conformational differences between the two forms of protein. However, neither the level of copper binding nor the level of SOD activity associated with this form of prion protein altered with the identity of codon 129. These results suggest that in the holo-metal binding form of the protein, prion structure but not its SOD activity is affected by polymorphism at codon 129.
Wong
B S
BS
NERC Institute of Virology and Environmental Microbiology, Mansfield Road, Oxford, OX1 3SR, United Kingdom.
Clive
C
C
Haswell
S J
SJ
Williamson
R A
RA
Burton
D R
DR
Gambetti
P
P
Sy
M S
MS
Jones
I M
IM
Brown
D R
DR
D000818:Animals; D001665:Binding Sites; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D011110:Polymorphism, Genetic; D011328:Prions / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D011994:Recombinant Proteins / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
D011328:Prions; D011994:Recombinant Proteins; D003300:Copper; D013482:Superoxide Dismutase