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Los heterodímeros Fos-Jun y los homodímeros Jun doblan el ADN en orientaciones opuestas: implicaciones para la

T K Kerppola¹, T Curran

¹Department of Molecular Oncology and Virology, Roche Institute of Molecular Biology, Nutley, New Jersey 07110.

|July 26, 1991

Resumen

Las proteínas Fos y Jun alteran la conformación de la hélice del ADN cuando se unen al sitio AP-1. Los heterodímeros Fos-Jun y los homodímeros Jun inducen distintas curvas de ADN, formando complejos únicos.

Área de la Ciencia:

Biología Molecular Biología Molecular
Biología Estructural Biología estructural.
La bioquímica es la bioquímica.

Sus antecedentes:

El sitio de unión del factor de transcripción AP-1 es crucial para regular la expresión génica.
Las proteínas Fos y Jun forman heterodímeros y homodímeros que se unen al sitio AP-1.
Comprender las consecuencias estructurales de estas interacciones es clave para descifrar la regulación génica.

Objetivo del estudio:

Investigar los cambios conformacionales inducidos en la hélice del ADN por los heterodímeros Fos-Jun y los homodímeros Jun.
Para determinar la orientación y la magnitud de la flexión del ADN mediada por estos complejos proteicos.
Para dilucidar cómo los diferentes dominios de las proteínas Fos y Jun contribuyen a la flexión del ADN.

Principales métodos:

Análisis de permutación circular para evaluar la flexión del ADN inducida por la unión a las proteínas.
Análisis de fase para determinar la orientación de la flexión del ADN (groove mayor o menor).
Uso de proteínas de longitud completa y péptidos truncados (dominios de dimerización y de unión al ADN) para mapear regiones funcionales.

Principales resultados:

Tanto los heterodímeros Fos-Jun como los homodímeros Jun inducen una flexión significativa en el sitio AP-1.
Los heterodímeros Fos-Jun doblan el ADN hacia la ranura mayor.
Los homodímeros Jun doblan el ADN hacia el surco menor, lo que indica orientaciones opuestas.
Los dominios específicos de proteínas influyen en la magnitud del ángulo de flexión del ADN.

Conclusiones:

Los heterodímeros Fos-Jun y los homodímeros Jun forman complejos de ADN-proteína topológicamente distintos a pesar de las similitudes de secuencia.
La orientación de la flexión del ADN es un determinante crítico de la formación y función compleja.
La flexión diferencial del ADN por los homodímeros Fos-Jun y Jun contribuye a la especificidad de la regulación génica.

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