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Yersinia YopJ acetila y inhibe la activación de la quinasa al bloquear la fosforilación
Sohini Mukherjee1, Gladys Keitany, Yan Li
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science (New York, N.Y.)
|May 27, 2006
Resumen
Yersinia fue una de ellas.
Área de la Ciencia:
- Microbiología y Biología Molecular.
- La señalización celular y la inmunología.
Sus antecedentes:
- Las especies de Yersinia emplean proteínas efectoras tipo III para interrumpir las vías de señalización de los eucariotas huéspedes.
- Las vías inmunitarias innatas clave, incluidas la proteína quinasa activada por mitógeno (MAPK) y el factor nuclear kappaB (NFkappaB), son objetivo de los efectores de Yersinia.
- El efector Yersinia YopJ inhibe específicamente la señalización de MAPK y NFkappaB al bloquear la activación de las MAPK quinasas (MAPKKs).
Objetivo del estudio:
- Para aclarar el mecanismo molecular por el cual el efector Yersinia YopJ inhibe la activación de MAPKK.
- Para investigar la actividad enzimática de YopJ y su papel en la modificación de las proteínas MAPKK.
- Para entender cómo la modificación mediada por YopJ impacta la fosforilación y la activación de las MAPKKs.
Principales métodos:
- Análisis bioquímicos para determinar la actividad enzimática de YopJ.
- Modificación in vitro de MAPKK6 utilizando YopJ y la acetil-coenzima A (CoA).
- Análisis de la modificación de los residuos de serina y treonina en el bucle de activación MAPKK6.
- Evaluación del impacto de la modificación de YopJ en la fosforilación y activación de MAPKK6.
Principales resultados:
- YopJ funciona como una acetiltransferasa, utilizando el acetil-CoA.
- YopJ acetila los residuos críticos de serina y treonina dentro del bucle de activación de MAPKK6.
- La acetilación por YopJ compite directamente con y previene la fosforilación de MAPKK6, inhibiendo así su activación.
Conclusiones:
- El efector YopJ de Yersinia inhibe la señalización inmune innata del huésped al acetilizar y bloquear la activación de MAPKK.
- Este mecanismo de acetilación sirve como una inhibición competitiva directa de la fosforilación, evitando la señalización aguas abajo.
- La modificación covalente a través de la acetilación representa un potencial mecanismo de regulación general en las vías de señalización biológica.
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