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El ensamblaje de un complejo de señalización GTPasa-cinasa por un andamio catalítico bacteriano
Andrey S Selyunin1, Sarah E Sutton, Bethany A Weigele
1Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8816, USA.
Nature
|December 21, 2010
Resumen
Efector enterohemorrágico de E. coli EspG actúa como un andamio catalítico, reprogramando la señalización de la célula huésped mediante la organización de complejos de GTPasa y quinasa. Esta proteína bacteriana inhibe la señalización de la GTPasa y activa las vías de la quinasa.
Área de la Ciencia:
- Microbiología Microbiología.
- Biología celular Biología celular.
- Biología Estructural Biología estructural.
Sus antecedentes:
- Las proteínas del andamio regulan el flujo de información celular mediante el ensamblaje de enzimas en circuitos de señalización.
- Las proteínas efectoras bacterianas pueden inhibir estos circuitos a través de modificaciones post-traducionales.
- Los patógenos pueden organizar directamente las redes de señalización del huésped utilizando el andamio enzimático, pero los efectores y los mecanismos a menudo son desconocidos.
Objetivo del estudio:
- Identificar efectores bacterianos que organizan redes de señalización de orden superior.
- Elucidar los mecanismos por los cuales estos efectores manipulan la señalización celular del huésped.
- Caracterice la base estructural para la función del efector.
Principales métodos:
- Cribado funcional para identificar las proteínas efectoras que regulan el tráfico endomembranar.
- Cristalografía para determinar las estructuras de complejos proteicos efector-hospedador.
- Pruebas bioquímicas para analizar la actividad enzimática y la inhibición.
Principales resultados:
- El efector de tipo III EspG de la Escherichia coli enterohemorrágica O157:H7 fue identificado como un regulador del tráfico endomembranar.
- EspG tiene como objetivo el factor de ribosilación ADP (ARF) GTPasas y quinasas activadas por p21 (PAKs).
- Los estudios estructurales revelaron que EspG inhibe la actividad de la GTPasa ARF y activa alostericamente la actividad de la PAK quinasa, actuando como un andamio catalítico para los complejos de señalización de la GTPasa-cinasa.
Conclusiones:
- La EspG funciona como un nuevo "armazón catalítico", que modula simultáneamente las vías de señalización de la GTPasa y la quinasa.
- Esta reprogramación de la señalización de la célula huésped por EspG proporciona un nuevo mecanismo para la patogénesis bacteriana.
- La comprensión de estas funciones efectoras ofrece información sobre la regulación de las redes de señalización celular.
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