La unión de la proteína priónica asociada a la enfermedad con el plasminógeno
M B Fischer1, C Roeckl, P Parizek
1Institute for Neuropatholgy, University Hospital of Zurich, Switzerland.
Nature
|December 2, 2000
Resumen
Los investigadores identificaron plasminógeno en la sangre que se une a la proteína priónica asociada a la enfermedad (PrPSc) pero no a la proteína priónica normal (PrPC). Este descubrimiento podría ayudar en el diagnóstico de las encefalopatías espongiformes transmisibles.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Las encefalopatías espongiformes transmisibles (ETS) están relacionadas con la acumulación de proteína priónica anormal (PrPSc), una forma mal plegada de la proteína priónica celular (PrPC).
- El mecanismo de la replicación de PrPSc y su interacción con los componentes celulares para causar neuropatología sigue siendo incompletamente entendido.
- Distinguir entre PrPC y PrPSc basado en la conformación ha sido un desafío significativo.
Objetivo del estudio:
- Para identificar los factores endógenos en la sangre que pueden discriminar entre PrPC y PrPSc.
- Investigar el papel de tales factores en la patogénesis de la enfermedad priónica y las posibles aplicaciones de diagnóstico.
Principales métodos:
- Cribado de sangre humana y de ratón para actividades que se unen a PrPSc pero no a PrPC.
- La identificación de la proteína específica responsable de esta actividad de unión.
- Caracterización de la interacción de unión mediante ensayos bioquímicos, incluida la interrupción con denaturantes y estudios de competencia.
Principales resultados:
- Identificó el plasminógeno, una pro-proteasa sanguínea, como una proteína que se une a PrPSc y la infectividad priónica, pero no a PrPC.
- Se demostró que la unión de PrPSc al plasminógeno es dependiente de la conformación, siendo abolida por la urea 6M o la guanidina.
- Se demostró que el sitio de unión a la lisina 1 del plasminógeno (kringles I-III) media esta unión específica, que puede competir con la lisina.
Conclusiones:
- El plasminógeno es el primer factor endógeno identificado que se une selectivamente al conformador PrPSc patológico sobre el PrPC normal.
- Esta propiedad de unión única del plasminógeno ofrece una vía potencial para el desarrollo de herramientas de diagnóstico para las EET.
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