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La estructura cristalina del dominio de unión al ADN del receptor de estrógeno unido al ADN: cómo los receptores

J W Schwabe¹, L Chapman, J T Finch

¹Medical Research Council Laboratory of Molecular Biology, Cambridge, England.

|November 5, 1993

Resumen

El dominio de unión al ADN del receptor de estrógeno forma un dímero para reconocer secuencias específicas de ADN. Esta visión estructural explica cómo los receptores de hormonas nucleares distinguen sus sitios de unión al ADN, un mecanismo aplicable a toda la familia de receptores.

Área de la Ciencia:

Biología Molecular Biología Molecular
Biología Estructural Biología estructural.
Genética La genética.

Sus antecedentes:

Los receptores de hormonas nucleares son factores cruciales de transcripción activados por ligandos.
Estos receptores regulan la expresión génica a través de la unión al ADN.
Comprender su reconocimiento de ADN es clave para su función.

Objetivo del estudio:

Determinar la estructura cristalina del dominio de unión al ADN del receptor de estrógeno complejo con el ADN.
Para dilucidar el mecanismo molecular de reconocimiento de secuencia específica de ADN por los receptores de hormonas nucleares.

Principales métodos:

Cristalografía de rayos X con una resolución de 2.4 Angstrom.
Análisis de la estructura del complejo proteína-ADN.

Principales resultados:

El dominio de unión al ADN del receptor de estrógeno forma un dímero simétrico en su sitio de unión al ADN palíndromo.
La estructura revela interacciones específicas que permiten el reconocimiento del medio sitio del receptor de estrógeno sobre el medio sitio del receptor de glucocorticoides estrechamente relacionado.

Conclusiones:

La estructura determinada proporciona un mecanismo general para el reconocimiento de la secuencia de ADN por la superfamilia de receptores de hormonas nucleares.
Este hallazgo tiene implicaciones para la comprensión de la regulación génica de esta importante clase de proteínas.

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