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Oligopeptide Competition Assay for Phosphorylation Site Determination
Published on: May 18, 2017
Estructura del factor de intercambio Epac2 sensible a la AMP cíclica en su estado autoinhibido
Holger Rehmann1, Joost Das, Puck Knipscheer
1Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Nature
|February 3, 2006
Resumen
Las proteínas de intercambio activadas directamente por la AMP cíclica (Epac) regulan los procesos celulares. El estudio revela la estructura autoinhibida de Epac2, detallando sus regiones reguladoras y catalíticas y un mecanismo para la activación mediada por cAMP.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
- La señalización celular de las células.
Sus antecedentes:
- Las proteínas Epac son factores de intercambio guanina-nucleótido (GEF) para las GTPasas Rap1 y Rap2.
- Están directamente regulados por la AMP cíclica (cAMP) e involucrados en la adhesión celular y la secreción de insulina.
Objetivo del estudio:
- Para determinar la estructura tridimensional del Epac2.2 de longitud completa.
- Para dilucidar el estado autoinhibido y el mecanismo de activación inducida por la cAMP.
Principales métodos:
- La cristalografía de rayos X fue utilizada para resolver la estructura de Epac2.
- Se realizó un análisis mutacional para investigar el mecanismo de activación.
Principales resultados:
- Se determinó la estructura de Epac2 de longitud completa en su estado autoinhibido.
- Se identificó una estructura de "tablero" y un "cerrojo iónico" como elementos inhibidores clave.
- Se propuso un modelo para la activación inducida por CAMP que involucra el movimiento rígido del cuerpo.
Conclusiones:
- La estructura revela cómo Epac2 es autoinhibido en ausencia de cAMP.
- Los hallazgos proporcionan información sobre el mecanismo universal de la activación de proteínas reguladas por cAMP.
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