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Control de la conformación de los aislados de proteínas del andamio Ste5 contra la desactivación de la quinasa MAP
Jesse G Zalatan1, Scott M Coyle, Saravanan Rajan
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
Science (New York, N.Y.)
|August 11, 2012
Resumen
La proteína del andamio de la levadura Ste5 previene la falta de comunicación en la vía de apareamiento no por secuestro, sino por una interacción intramolecular. Las señales de feromonas liberan esta autoinhibición, permitiendo la transmisión de la señal de apareamiento.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología molecular La biología molecular.
- Transducción de señales de transducción de señales.
Sus antecedentes:
- Las células utilizan proteínas de señalización a través de múltiples vías, arriesgando el diálogo cruzado.
- Se supone que las proteínas del andamio evitan la falta de comunicación a través del secuestro de proteínas.
- La vía de la proteína quinasa activada por mitógeno (MAPK) de apareamiento de la levadura se basa en la proteína del andamio Ste5.
Objetivo del estudio:
- Investigar el mecanismo por el cual la proteína del andamio Ste5 evita la falta de comunicación en la vía de apareamiento de la levadura MAPK.
- Para determinar si Ste5 utiliza secuestro u otro mecanismo para regular la actividad de la vía.
Principales métodos:
- Análisis de las interacciones y conformaciones de la proteína Ste5.
- Investigar el papel de las interacciones intramoleculares dentro de la Etapa 5.5.
- Estudiando el efecto de la señalización de feromonas en la función Ste5.
Principales resultados:
- Ste5 no impide la activación de la vía de apareamiento a través del secuestro de proteínas.
- Una interacción intramolecular entre la homología de pleckstrin (PH) de Ste5 y los dominios de von Willebrand tipo A (VWA) inhibe la activación de Fus3 MAPK en condiciones basales.
- La unión a la membrana inducida por feromonas libera esta autoinhibición, permitiendo la transmisión de la señal.
Conclusiones:
- Ste5 emplea un mecanismo conformacional, no de secuestro, para controlar la actividad de la vía de apareamiento.
- Ste5 actúa como un sensor directo de las señales de feromonas, regulando la transmisión de la señal a la vía MAPK de apareamiento.
- Este mecanismo asegura un control preciso sobre la respuesta de apareamiento de la levadura.
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