We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Strain-specific prion-protein conformation determined by metal ions.
- Authors
Wadsworth, Jonathan D.F.; Hill, Andrew F.; Joiner, Susan; Jackson, Graham S.; Clarke, Anthony R.; Collinge, John
- Abstract
In animals infected with a transmissible spongiform encephalopathy, or prion disease, conformational isomers (known as PrP[SUPSc] proteins) of the wild-type, host-encoded cellular prion protein (PrP[SUPc]) accumulate. The infectious agents, prions, are composed mainly of these conformational isomers, with distinct prion isolates or strains being associated with different PrP[SUPSc] conformations and patterns of glycosylation. Here we show that two different human PrP[SUPSc] types, seen in clinically distinct subtypes of classical Creutzfeldt-Jakob disease, can be interconvertedin vitro by altering their metal-ion occupancy. The dependence of PrP[SUPSc] 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.
- Subjects
PRION diseases in animals; CONFORMATIONAL analysis; MOLECULAR biology
- Publication
Nature Cell Biology, 1999, Vol 1, Issue 1, p55
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/9030