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La base molecular para la importación de azúcar en parásitos de la malaria
Abdul Aziz Qureshi1, Albert Suades1, Rei Matsuoka1
1Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Nature
|January 31, 2020
Resumen
El parásito de la malaria
Área de la Ciencia:
- Biología estructural
- Parasitología
- La bioquímica
Sus antecedentes:
- Los transportadores de glucosa de mamíferos (GLUT) están especializados.
- El transportador de hexosa de Plasmodium falciparum 1 (PfHT1) transporta tanto la glucosa como la fructosa.
- Comprender la promiscuidad del azúcar de PfHT1 es crucial para el metabolismo del parásito de la malaria.
Objetivo del estudio:
- Para determinar la estructura cristalina de PfHT1.
- Para aclarar la base molecular de la promiscuidad del sustrato de PfHT1.
- Comprender el mecanismo de acoplamiento entre la unión de azúcar y el encierro de transporte.
Principales métodos:
- Cristalografía de rayos X de PfHT1 complejado con D-glucosa.
- Mutagénesis dirigida al sitio de PfHT1.
- Comparación estructural con los transportadores de GLUT de los mamíferos.
Principales resultados:
- El sitio de unión de azúcares de PfHT1 es similar a los transportadores de GLUT.
- Las mutaciones que imitan los sitios de unión a GLUT no alteraron la preferencia por el azúcar de PfHT1.
- La hélice TM7b en PfHT1 adopta una conformación ocluida, revelando la dinámica de entrada del sustrato.
- El acoplamiento alostérico entre la unión de azúcar y el gating implica contactos polares entre TM7b y TM1.
Conclusiones:
- PfHT1 logra la promiscuidad del sustrato a través de una dinámica de entrada de sustrato evolucionada, no de sitios de unión alterados.
- Los contactos polares entre las hélices de transmembrana son críticos para el transporte.
- Este estudio proporciona un mecanismo molecular para el transporte de azúcar en los parásitos de la malaria.
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