Nature Cell Biology
1, 55 - 59 (1999)
doi:10.1038/9030
Strain-specific prion-protein conformation determined by metal ionsJonathan D.F. Wadsworth1, Andrew F. Hill1, Susan Joiner1, Graham S. Jackson1, Anthony R. Clarke1, 2
& John Collinge11
MRC Prion Unit and Department of Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, UK 2
Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK
Correspondence should be addressed to John Collinge j.collinge@ic.ac.ukIn animals infected with a transmissible spongiform encephalopathy, or
prion disease, conformational isomers (known as PrPSc proteins)
of the wild-type, host-encoded cellular prion protein (PrPC)
accumulate. The infectious agents, prions, are composed mainly of these conformational
isomers, with distinct prion isolates or strains being associated with different
PrPSc conformations and patterns of glycosylation. Here we
show that two different human PrPSc types, seen in clinically
distinct subtypes of classical Creutzfeldt−Jakob disease, can be interconverted
in vitro by altering their metal-ion occupancy. The dependence of PrP
Sc conformation on the binding of copper and zinc represents a new
mechanism for post-translational modification of PrP and for the generation
of multiple prion strains, with widespread implications for both the molecular
classification and the pathogenesis of prion diseases in humans and animals.
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