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Bases estructurales de la iniciación de la transcripción
Yu Zhang1, Yu Feng, Sujoy Chatterjee
1Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
Science (New York, N.Y.)
|October 23, 2012
Resumen
Este estudio revela las estructuras cristalinas de los complejos de iniciación de transcripción de la ARN polimerasa (RNAP). Estas estructuras detallan cómo el RNAP y el factor sigma (σ) reconocen los elementos de ADN promotor para la iniciación de la transcripción.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La iniciación de la transcripción es un paso regulador crítico en la expresión génica.
- La ARN polimerasa (RNAP) forma un complejo abierto con el ADN promotor para comenzar la transcripción.
- Comprender la base estructural de este proceso es clave para descifrar la regulación génica.
Objetivo del estudio:
- Para determinar las estructuras cristalinas de alta resolución de los complejos funcionales de iniciación de transcripción.
- Para dilucidar las interacciones moleculares entre RNAP, el factor sigma (σ) y el ADN promotor.
- Proporcionar información sobre el mecanismo de reconocimiento del promotor y el desenrollamiento del ADN.
Principales métodos:
- Se empleó cristalografía de rayos X para determinar las estructuras.
- Se utilizaron complejos de iniciación de transcripción funcional de la ARN polimerasa de Thermus thermophilus, σ(A), y el ADN promotor.
- Las estructuras se resolvieron en 2.9 y 3.0 Å de resolución.
Principales resultados:
- Las estructuras cristalinas revelan interacciones específicas de σ con el elemento -10 y el elemento discriminador, que implican la desestabilización de la base de ADN y la inserción de bolsillo.
- Se identificaron interacciones de RNAP con la región -4/+2, incluyendo la inserción de la base +2 en un bolsillo de RNAP.
- Se demostró que las interacciones entre σ y el ADN de cadena única de la hebra de la plantilla (ssDNA) preorganizan el ssDNA para el centro activo de RNAP.
Conclusiones:
- Las estructuras determinadas proporcionan una visión molecular detallada del reconocimiento del promotor durante la iniciación de la transcripción.
- Estos hallazgos ponen de relieve los roles precisos de σ y RNAP en la unión y desenrollo del ADN promotor.
- El estudio ofrece una base estructural para comprender cómo los complejos de iniciación de la transcripción están pre-organizados para una participación eficiente del ADN.
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