Binding of disease-associated prion protein to plasminogen

Michael B. Fischer, Christiane Roeckl, Petra Parizek, Hans Peter Schwarz and Adriano Aguzzi ()
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Michael B. Fischer: Institute for Neuropathology, University Hospital of Zurich
Christiane Roeckl: Institute for Neuropathology, University Hospital of Zurich
Petra Parizek: Institute for Neuropathology, University Hospital of Zurich
Hans Peter Schwarz: Baxter Hyland Immuno
Adriano Aguzzi: Institute for Neuropathology, University Hospital of Zurich

Nature, 2000, vol. 408, issue 6811, 479-483

Abstract: Abstract Transmissible spongiform encephalopathies are associated with accumulation of PrPSc, a conformer of a cellular protein called PrPC. PrPSc is thought to replicate by imparting its conformation onto PrPC (ref. 1), yet conformational discrimination between PrPC and PrPSc has remained elusive. Because deposition of PrPSc alone is not enough to cause neuropathology2, PrPSc probably damages the brain by interacting with other cellular constituents. Here we find activities in human and mouse blood which bind PrPSc and prion infectivity, but not PrPC. We identify plasminogen, a pro-protease implicated in neuronal excitotoxicity3,4, as a PrPSc-binding protein. Binding is abolished if the conformation of PrPSc is disrupted by 6M urea or guanidine. The isolated lysine binding site 1 of plasminogen (kringles I–III) retains this binding activity, and binding can be competed for with lysine. Therefore, plasminogen represents the first endogenous factor discriminating between normal and pathological prion protein. This unexpected property may be exploited for diagnostic purposes.

Date: 2000
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DOI: 10.1038/35044100

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