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Estructura de los dominios de unión al ADN de NFAT, Fos y Jun unidos específicamente al ADN
L Chen1, J N Glover, P G Hogan
1Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. lchen@xta1200.harvard.edu
Nature
|March 24, 1998
Resumen
El Factor Nuclear de las células T activadas (NFAT) y las proteínas AP-1 se unen al ADN para activar los genes inmunes. El análisis estructural revela su compleja interacción, formando una ranura para el reconocimiento del ADN.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Inmunología Inmunología.
- Biología Estructural Biología estructural.
Sus antecedentes:
- El Factor Nuclear de las células T activadas (NFAT) y AP-1 (Fos-Jun) son factores de transcripción.
- Se unen cooperativamente al ADN y activan los genes de respuesta inmune.
Objetivo del estudio:
- Para aclarar la base estructural de NFAT y AP-1 de unión cooperativa al ADN.
- Comprender el mecanismo de la activación sinérgica de los genes.
Principales métodos:
- Cristalografía de rayos X con una resolución de 2.7-A.
- Análisis de un complejo cuaternario de NFAT, Fos, Jun y un fragmento de ADN promotor del gen IL-2.
Principales resultados:
- Se determinó una estructura detallada de los dominios de unión al ADN de NFAT, Fos y Jun en complejo con el ADN.
- Se observó una interfaz extendida entre NFAT y AP-1.
- La flexión de Fos y ADN facilita esta interacción.
- El complejo forma una ranura continua para reconocer 15 pares de bases de ADN.
Conclusiones:
- Los datos estructurales revelan cómo se asocian NFAT y AP-1 en el ADN.
- Esta estrecha asociación es crucial para la activación sinérgica de la expresión génica inmune.
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