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La carga del ribosoma en la tapa del ARNm es impulsada por el acoplamiento conformacional entre eIF4G y eIF4E.
John D Gross1, Nathan J Moerke, Tobias von der Haar
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|December 17, 2003
Resumen
El factor de iniciación eucariota 4G (eIF4G) se une a eIF4E y la tapa de ARNm, formando una pulsera molecular. Esta estructura mejora la iniciación de la traducción y es vital para el crecimiento celular.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
- Regulación de la expresión génica Regulación de la expresión génica
Sus antecedentes:
- El factor de iniciación eucariota 4G (eIF4G) es central para la iniciación de la traducción, controlando la expresión génica.
- eIF4G interactúa con eIF3 y el complejo eIF4E/cap-mRNA para facilitar la carga del ribosoma en el mRNA.
- La traducción dependiente de la capa es un proceso crítico para la síntesis de proteínas.
Objetivo del estudio:
- Para determinar la estructura de la solución del complejo entre la levadura eIF4E/cap y un fragmento de eIF4G (393-490).
- Para aclarar el mecanismo por el cual eIF4G y eIF4E interactúan para regular la iniciación de la traducción.
Principales métodos:
- Determinación de la estructura de la solución del complejo eIF4E/cap y eIF4G (393-490).
- Análisis de las consecuencias estructurales de la unión a ambas proteínas.
Principales resultados:
- La unión de eIF4G (393-490) a eIF4E/cap induce una transición de plegado acoplado.
- Se forma un "brazalete molecular" estable, con eIF4G (393-490) formando un anillo helicoidal alrededor del extremo N de eIF4E.
- Este plegamiento conjunto mejora alostericamente la asociación de eIF4E con el cap. de ARNm.
Conclusiones:
- La interacción eIF4G-eIF4E y la estructura resultante son cruciales para el crecimiento celular óptimo y la distribución del polisoma.
- El complejo de ribonucleoproteína mensajera estable (mRNP) facilita múltiples rondas de carga ribosómica, lo que afecta las tasas de síntesis de proteínas.
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