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Dinámica de la liberación de iones pirofosfato y su movimiento acoplado del bucle de activación de estado cerrado a
Lin-Tai Da1, Dong Wang, Xuhui Huang
1Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Journal of the American Chemical Society
|December 31, 2011
Resumen
La liberación del ion pirofosfato (PP(i)) de la ARN polimerasa II (pol II) es crucial para la transcripción. Las simulaciones de dinámica molecular revelan residuos específicos, como H1085, K752 y K619, que facilitan la liberación de PP a través de un mecanismo de salto.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La biofísica es la biofísica.
- Biología computacional Biología computacional.
Sus antecedentes:
- La ARN polimerasa II (pol II) requiere la liberación de iones pirofosfato (PP ((i)) para el alargamiento de la transcripción.
- Las funciones precisas de los residuos de pol II y el bucle de activación en la liberación de PP (i) no se comprenden completamente.
Objetivo del estudio:
- Para aclarar el mecanismo de la liberación de PP (i) durante el alargamiento de la transcripción pol II.
- Investigar el papel del bucle gatillo y los residuos específicos de pol II en la liberación de PP.
Principales métodos:
- Simulaciones de dinámica molecular de todos los átomos (DM) en disolvente explícito.
- Construcción de un modelo de estado de Markov (MSM) para analizar las vías de liberación de PP.
- Simulaciones de mutante único para evaluar la función de los residuos clave.
Principales resultados:
- El bucle de activación exhibe un aumento del movimiento después de la catálisis, lo que ayuda a la liberación de PP (i) a través de interacciones H1085.
- PP(i) sale del sitio activo a través de un mecanismo de salto que involucra residuos conservados (K752, K619).
- Se identificaron cuatro estados cinéticamente metestables para el tránsito de PP (i) a través del canal secundario.
Conclusiones:
- H1085 y K752 facilitan la salida de PP (i) del sitio activo, mientras que K619 ayuda al paso a través del canal secundario.
- La liberación de PP(i) puede promover la apertura del bucle de activación, aunque las dinámicas de PP(i) son más rápidas.
- Los resultados de la simulación ofrecen predicciones para la validación experimental.
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