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Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta
Published on: December 5, 2019
Estructura de una ligasa RING E3 y E2 cargado de ubiquitina preparado para la catálisis
Anna Plechanovová1, Ellis G Jaffray, Michael H Tatham
1Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Nature
|July 31, 2012
Resumen
Este estudio revela el mecanismo estructural de la transferencia de ubiquitina por las ligasas RING E3. La estructura cristalina muestra cómo RNF4 y UbcH5A cooperan para posicionar la ubiquitina para una catálisis eficiente, aclarando un paso clave en la ubiquitinación.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La modificación de la ubiquitina es crucial para los procesos celulares y está mediada por las ligasas E3.
- Las ligasas RING E3 facilitan la transferencia de ubiquitina mediante la unión de sustratos y enzimas conjugadoras E2.
- El mecanismo preciso de la transferencia de ubiquitina por las ligasas RING E3 sigue siendo poco conocido.
Objetivo del estudio:
- Para dilucidar el mecanismo estructural de la transferencia de ubiquitina mediada por las ligasas RING E3.
- Proporcionar información a nivel atómico sobre la interacción entre RNF4, UbcH5A y ubiquitin.
Principales métodos:
- Determinación de la estructura cristalina del dominio RING dimérico de la rata RNF4 en complejo con E2 (UbcH5A) y ubiquitin.
- Análisis de la intrincada red de interacciones que estabilizan el complejo y posicionan la ubicuidad.
Principales resultados:
- La estructura cristalina revela que la ubiquitina está en contacto con ambos protómeros del dominio RING dimérico, mientras que E2 sólo entra en contacto con uno.
- La cola carboxiterminal de la ubiquitina está bloqueada en la ranura del sitio activo E2, induciendo cambios conformacionales.
- Esta disposición específica prepara el sitio activo E2 para la catálisis al facilitar la desprotonación y la estabilización del estado de transición.
Conclusiones:
- La estructura reportada proporciona una base mecanicista para la transferencia de ubiquitina por las ligasas RING E3.
- Este hallazgo aclara cómo las ligasas E3 posicionan con precisión la ubiquitina para una modificación eficiente del sustrato.
- El estudio ofrece información sobre la regulación de las enzimas conjugadoras E2 por las ligasas E3.
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