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Una aspartil proteasa dirige las proteínas efectoras de la malaria a la célula huésped
Justin A Boddey1, Anthony N Hodder, Svenja Günther
1The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia.
Nature
|February 5, 2010
Resumen
El parásito de la malaria Plasmodium falciparum exporta proteínas utilizando un motivo específico. Los investigadores identificaron la plasmepsina V (PMV) como la proteasa esencial para la escisión de este motivo, lo que permite la supervivencia del parásito y ofrece un nuevo objetivo terapéutico.
Área de la Ciencia:
- La parasitología molecular.
- Enfermedades infecciosas Las enfermedades infecciosas.
- Biología de los eritrocitos.
Sus antecedentes:
- Plasmodium falciparum causa malaria severa mediante la remodelación de los eritrocitos infectados.
- La supervivencia del parásito depende de la exportación de proteínas efectoras más allá de la vacuola.
- Las proteínas exportadas comparten un motivo pentamérico conservado (RxLxE/Q/D) escindido por una proteasa desconocida.
Objetivo del estudio:
- Para identificar la proteasa responsable de la escisión del motivo de exportación pentamérico en Plasmodium falciparum.
- Para aclarar el papel de esta proteasa en la remodelación de los eritrocitos y la virulencia de los parásitos.
Principales métodos:
- Análisis bioquímicos para identificar la actividad de la proteasa.
- La manipulación genética de Plasmodium falciparum.
- Análisis de la exportación de proteínas y el procesamiento N-terminal.
Principales resultados:
- La plasmepsina V (PMV), una proteasa aspática residente en ER, fue identificada como la proteasa responsable.
- PMV divide el motivo RxLxE/Q/D, revelando la señal de exportación del N-terminal (xE/Q/D).
- La actividad del PMV es esencial para la exportación de proteínas y está vinculada a otros eventos críticos de exportación, a diferencia del procesamiento de la peptidasa de señal.
Conclusiones:
- La plasmepsina V es esencial para la exportación de las proteínas efectoras de Plasmodium falciparum a los eritrocitos.
- La escisión mediada por PMV es un paso crítico para la virulencia de los parásitos.
- El PMV representa un nuevo objetivo terapéutico para el tratamiento de la malaria.
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