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Un emparejamiento inusual de bases durante la decodificación de un codón stop por el ribosoma
Israel S Fernández1, Chyan Leong Ng, Ann C Kelley
1MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Nature
|July 2, 2013
Resumen
La modificación de la pseudouridina permite que el ARN de transferencia (ARNt) lea los codones de parada, lo que requiere un emparejamiento de bases inusual. Este estudio estructural revela el ribosoma.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
- Genética La genética.
Sus antecedentes:
- La síntesis de proteínas normalmente termina con el reconocimiento de los codones de parada (UGA, UAA, UAG) por los factores de liberación.
- El ARN de transferencia (ARNt) puede leer a través de los codones de parada si la uridina inicial se modifica a pseudouridina (Ψ).
- Esta lectura a través requiere la formación de pares de bases purina-purina no canónicos, que normalmente no están permitidos.
Objetivo del estudio:
- Para dilucidar la base estructural para detener la lectura de codones mediada por el tRNA. modificado por pseudouridina.
- Investigar la capacidad del centro de decodificación ribosómica para acomodar pares de bases no canónicos durante la traducción.
Principales métodos:
- Se determinó la estructura cristalina de la subunidad ribosómica 30S compleja con el bucle del tallo anticodón del tRNA ((Ser) unido a un codón de parada ΨAG.
- Utilizó cristalografía de rayos X a una resolución de 3.1 Å.
Principales resultados:
- La estructura reveló un par de bases ΨA en la primera posición del codón.
- Se observaron inusuales pares de bases purina-purina con una geometría Watson-Crick/Hoogsteen en la segunda y tercera posición del codón.
- El centro de decodificación ribosómica demostró una capacidad inesperada para acomodar estos pares de bases no canónicos.
Conclusiones:
- La modificación pseudouridina de los codones stop permite la unión y lectura del tRNA a través de la formación de pares de bases no canónicas.
- El centro de decodificación ribosómica posee una flexibilidad inherente para acomodar geometrías de emparejamiento de bases inusuales, desafiando suposiciones anteriores.
- Esta visión estructural proporciona una comprensión molecular de los mecanismos de control traslacional que involucran nucleósidos modificados.
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