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La estructura atómica de la APC/C y su mecanismo de ubiquitinación de proteínas
Leifu Chang1, Ziguo Zhang1, Jing Yang1
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Nature
|June 18, 2015
Resumen
El estudio estructural del complejo promotor de anafase (APC/C) revela cómo Emi1 inhibe las enzimas E2 y define las interacciones Cdh1. Esto proporciona un marco para la comprensión de la regulación APC/C en la división celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
Sus antecedentes:
- El complejo promotor de anafase (APC/C) es una ligasa de ubiquitina E3 crucial que regula las transiciones del ciclo celular.
- La actividad APC/C está estrechamente controlada por los coactivadores, la fosforilación y las proteínas de punto de control.
Objetivo del estudio:
- Para determinar las estructuras atómicas de los complejos APC/C-coactivador.
- Aclarar los mecanismos de la inhibición de APC/C por Emi1 y la regulación por Cdh1.
- Para obtener información sobre la reacción de ubiquitinación mediada por APC/C.
Principales métodos:
- Se empleó la microscopía crioectrónica (cryo-EM) para obtener estructuras de alta resolución.
- Análisis estructural de los complejos APC/C con conjugados de Emi1 y UbcH10-ubiquitina.
Principales resultados:
- Se determinaron las estructuras atómicas de los complejos APC/C-Emi1 y APC/C-UbcH10-ubiquitina.
- Las estructuras revelan la arquitectura de las subunidades APC/C y el módulo catalítico.
- Se definieron los mecanismos de la inhibición mediada por Emi1 de UbcH10 y Ube2S.
- Se aclararon las interacciones de Cdh1 y el impacto de la fosforilación de Cdh1.
- Se obtuvieron información sobre el inicio de la ubiquitinación por APC/C.
Conclusiones:
- El estudio proporciona una comprensión estructural detallada de la regulación APC/C.
- Estos hallazgos ofrecen un marco cuantitativo para futuros estudios in vivo de la función APC/C.
- Los resultados avanzan en nuestro conocimiento del control del ciclo celular y la segregación cromosómica.
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