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Las estructuras de APC/C(Cdh1) con sustratos identifican a Cdh1 y Apc10 como el co-receptor de la caja D
Paula C A da Fonseca1, Eric H Kong, Ziguo Zhang
1Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.
Nature
|November 26, 2010
Resumen
Los investigadores utilizaron microscopía criolectrónica para revelar cómo el complejo promotor de anafase (APC/C) reconoce las proteínas objetivo a través de motivos de destrucción. Este estudio aclara la base estructural para la ubicuidad del sustrato APC/C, crucial para el control del ciclo celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Estructural Biología estructural.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El complejo promotor de la anafase (APC/C) regula la división celular mediante la ubicuidad de proteínas clave.
- El reconocimiento de objetivos por APC/C depende de motivos de destrucción como el D-box.
- Los mecanismos estructurales de la unión al sustrato APC/C y la ubicuidad siguen sin estar claros.
Objetivo del estudio:
- Aclarar las bases estructurales del reconocimiento de sustratos por el APC/C.
- Investigar el papel de las proteínas coactivadoras (Cdc20, Cdh1) y las subunidades APC/C del núcleo en la selección del objetivo.
- Comprender las interacciones estructurales involucradas en el reconocimiento de D-box.
Principales métodos:
- Microscopía electrónica de una sola partícula (cryo-EM) para determinar la estructura del complejo APC/C(Cdh1).
- Espectroscopia de Resonancia Magnética Nuclear (RMN) para analizar las interacciones D-box-Apc10.
- Mapeo de diferencias para identificar componentes dentro del complejo APC/C.
Principales resultados:
- Se determinó un mapa cryo-EM de la levadura en ciernes APC/C(Cdh1) unido a un péptido D-box a una resolución de ~10 Å.
- Se identificó un módulo catalítico y de reconocimiento de sustratos, compuesto por Cdh1, Apc10 y Apc2, en la cavidad central de APC/C.
- Las interacciones específicas de la caja D-Apc10 fueron confirmadas por RMN, destacando el papel de Apc10 en el reconocimiento de la caja D.
Conclusiones:
- El estudio proporciona un marco estructural para el reconocimiento y la catálisis del sustrato APC/C.
- Aclara las funciones combinadas del coactivador (Cdh1) y las subunidades centrales APC/C (Apc10) en el reconocimiento de D-box.
- Este trabajo promueve la comprensión de los mecanismos de control del ciclo celular mediados por el APC / C.
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