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Consequences of manganese replacement of copper for prion protein function and proteinase resistance
Author(s) -
Brown David R.,
Hafiz Farida,
Glasssmith Leslie L.,
Wong BoonSeng,
Jones Ian M.,
Clive Christine,
Haswell Stephen J.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.6.1180
Subject(s) - biology , manganese , copper , resistance (ecology) , function (biology) , prion protein , virology , microbiology and biotechnology , genetics , biochemistry , medicine , ecology , metallurgy , disease , materials science
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.