Binding of disease-associated prion protein to plasminogen

被引:180
作者
Fischer, MB
Roeckl, C
Parizek, P
Schwarz, HP
Aguzzi, A [1 ]
机构
[1] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland
[2] Baxter Hyland Immuno, A-1221 Vienna, Austria
关键词
D O I
10.1038/35044100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 neuropathology(2), PrPSc probably damages the brain by interacting with other cellular constituents. Here we rnd activities in human and mouse blood which bind PrPSc and prion infectivity, but not PrPC. We identify plasminogen, a pro-protease implicated in neuronal excitotoxicity(3,4), 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.
引用
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页码:479 / 483
页数:6
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