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Purificación del componente A de la Rab geranylgeranyl transferasa: posible identidad con el producto del gen de la
M C Seabra1, M S Brown, C A Slaughter
1Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Cell
|September 18, 1992
Resumen
La geranilgeraniltransferasa de Rab (GG transferasa) es crucial para la unión del geranilgeranil a las proteínas de Rab. Su componente A muestra similitudes con una proteína vinculada a la coroideremia, lo que sugiere una causa potencial para esta degeneración de la retina.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- La neurociencia es la neurociencia.
Sus antecedentes:
- La Rab geranylgeranyl transferasa (GG transferasa) es una enzima clave en la modificación post-traduccional.
- Se compone de dos componentes, A y B, con el componente B que contiene 60 y 38 kd polipéptidos.
Objetivo del estudio:
- Para purificar y caracterizar el componente A del cerebro de rata GG transferasa.
- Para investigar el papel de la GG transferasa en la modificación de las proteínas de unión a Rab GTP.
- Para explorar el vínculo potencial entre la GG transferasa y la coroideremia.
Principales métodos:
- Purificación del componente A (95 kd polipéptido).
- Ensayos enzimáticos para estudiar la geranilación de Rab3A y Rab1A.
- Mutagénesis dirigida al sitio de las cisteínas Rab1A COOH-terminales.
- Secuenciación de péptidos y comparación con proteínas conocidas.
Principales resultados:
- El componente A fue purificado como un único polipéptido de 95 kd.
- La holoenzima une geranilgeranilo a las cisteínas en Rab3A y Rab1A.
- La mutación de las cisteínas terminales de COOH en Rab1A abolió la reacción e inhibió la geranilación de tipo salvaje de Rab.
- Los péptidos del componente A mostraron similitud con el producto genético de la coroideremia.
Conclusiones:
- El componente A probablemente se une a las proteínas Rab a través de secuencias conservadas.
- El Componente B es responsable de la transferencia de geranil-geranil.
- Los defectos en esta vía de transferasa GG pueden causar coroideremia, una degeneración de la retina ligada al X.
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