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Mutaciones que alteran la estructura de las secuencias de codificación similares al factor de crecimiento epidérmico
M R Kelley1, S Kidd, W A Deutsch
1Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021.
Cell
|November 20, 1987
Resumen
El estudio revela que las repeticiones específicas similares al factor de crecimiento epidérmico (EGF) dentro de la proteína Drosophila Notch tienen funciones distintas. Las variaciones en estas repeticiones y su número total son cruciales para la proteína Notch.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Genética molecular La genética molecular.
- La neurociencia es la neurociencia.
Sus antecedentes:
- La proteína Drosophila Notch es un regulador clave de la neurogénesis.
- Comprende numerosos dominios repetidos en tándem similares al factor de crecimiento epidérmico (similar al FEAG).
- Se sabe que estas repeticiones similares a las del FEAG son críticas para la señalización de Notch.
Objetivo del estudio:
- Investigar la diferenciación funcional entre las 36 repeticiones similares al EGF en la proteína Notch.
- Para determinar la importancia del número de repeticiones y la variación de la secuencia para la función de la proteína Notch.
- Para aclarar los roles de regiones específicas de repetición similares al FEAG en las interacciones de proteínas.
Principales métodos:
- Análisis de ocho mutaciones específicas que causan sustituciones de un solo aminoácido en elementos homólogos del FEAG.
- Análisis genéticos de estas mutaciones en Drosophila.
- Comparación de secuencias de ADN de moscas mutantes y de tipo salvaje.
Principales resultados:
- Evidencia de diferenciación funcional entre secuencias similares al FEA repetidas en tándem.
- Demostración de que el número total de repeticiones y las variaciones menores de la secuencia son vitales para la función Notch de tipo salvaje.
- Identificación de regiones distintas de repeticiones similares a las del FEAG involucradas en la dimerización/multimerización e interacción con el potenciador de la escisión.
Conclusiones:
- Las repeticiones similares al FEAG dentro de la proteína Notch no son funcionalmente redundantes.
- Las secuencias de repetición específicas y su recuento total son críticos para la actividad adecuada de la proteína Notch.
- Diferentes conjuntos de repeticiones similares al EGF median distintas interacciones proteína-proteína esenciales para la neurogénesis.
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