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RanGAP media en la hidrólisis de GTP sin un dedo de arginina
Michael J Seewald1, Carolin Körner, Alfred Wittinghofer
1Max-Planck-Institut für molekulare Physiologie, Abteilung Strukturelle Biologie, Dortmund, Germany.
Nature
|February 8, 2002
Resumen
Las proteínas activadoras de la proteína de unión al nucleótido de guanina (GAP) suelen utilizar un mecanismo de dedo de arginina. Sin embargo, RanGAP, que activa Ran GTPase, no emplea esta estrategia.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Las proteínas activadoras de la proteína de unión al nucleótido de guanina (GAPs) aceleran la hidrólisis de GTP en las proteínas G.
- El mecanismo del "dedo de la arginina" es un modelo universal propuesto para la acción de GAP, aclarado a través de estudios sobre Ras y Rho.
- Ran, una proteína nuclear relacionada con Ras, regula el transporte nucleocitoplasmático y los procesos mitóticos, con su forma unida al GTP hidrolizada por RanGAP y RanBP1.
Objetivo del estudio:
- Para dilucidar el mecanismo de la hidrólisis de GTP mediada por RanGAP.
- Para investigar las bases estructurales de la función del complejo ternario RanGAP-RanBP1-Ran.
- Para determinar si RanGAP utiliza el mecanismo del dedo de arginina conservado.
Principales métodos:
- Determinación estructural tridimensional del complejo ternario Ran-RanBP1-RanGAP en estados básicos y de transición.
- Experimentos bioquímicos para evaluar el mecanismo de la hidrólisis de GTP.
Principales resultados:
- La estructura del complejo Ran-RanBP1-RanGAP revela que RanGAP no emplea un dedo de arginina.
- Los datos bioquímicos indican que Ran en sí mismo proporciona la maquinaria central para la hidrólisis rápida de GTP.
- El residuo catalítico de glutamina dentro de Ran es esencial para la catálisis, lo que requiere un posicionamiento correcto.
Conclusiones:
- La hidrólisis de GTP mediada por RanGAP diverge del mecanismo establecido del dedo de la arginina visto en Ras y Rho.
- La actividad intrínseca de la GTPasa de Ran, facilitada por RanGAP y RanBP1, es crucial para su función.
- Las perspectivas estructurales y bioquímicas destacan la importancia del posicionamiento preciso de los residuos catalíticos en la regulación de la GTPasa.
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