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Estructura, función y conformaciones inducidas por el activador del coactivador CRSP
Dylan J Taatjes1, Anders M Näär, Frank Andel
1Howard Hughes Medical Institute and, Lawrence Berkeley National Laboratory, Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley, CA 94720, USA.
Science (New York, N.Y.)
|February 9, 2002
Resumen
El complejo de cofactor reclutado por el activador (ARC) se separa en dos partes: ARC-L y el cofactor requerido para la activación de Sp1 (CRSP). CRSP es el cofactor de transcripción activo, que muestra conformaciones distintas influenciadas por activadores.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
- Regulación genética Reglamento genético.
Sus antecedentes:
- Se sabe que los complejos de cofactores humanos ARC y CRSP median la transcripción dependiente del activador in vitro.
- La relación estructural y funcional entre ARC y CRSP, a pesar de las subunidades compartidas, sigue sin estar clara.
Objetivo del estudio:
- Investigar la relación estructural y funcional entre los complejos de cofactores ARC y CRSP.
- Determinar las funciones individuales de los subcomplejos ARC en la regulación transcripcional.
Principales métodos:
- Purificación por afinidad del complejo ARC.
- Separación bioquímica del ARC en subcomplejos ARC-L y CRSP.
- Pruebas de transcripción in vitro.
- Microscopía electrónica (EM) y reconstrucción 3D para el análisis estructural.
Principales resultados:
- ARC purificado por afinidad comprende dos complejos distintos: ARC-L y CRSP.
- El CRSP es transcripcionalmente activo, mientras que el ARC-L es inactivo.
- El análisis de EM reveló diferencias estructurales significativas entre ARC-L y CRSP.
- CRSP exhibió distintas conformaciones inducidas por el activador.
Conclusiones:
- El CRSP es el coactivador funcional, distinto del complejo inactivo ARC-L.
- Los cambios conformacionales inducidos por el activador en la CRSP son probablemente clave para su potenciación transcripcional.
- Este estudio aclara la composición de las subunidades y las funciones funcionales dentro de la maquinaria de transcripción ARC/CRSP.
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