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Las estructuras cristalinas de un transportador multidrogas revelan un mecanismo de rotación funcional

Satoshi Murakami¹, Ryosuke Nakashima, Eiki Yamashita

¹Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan. mura@sanken.osaka-u.ac.jp

|August 18, 2006

Resumen

El transportador de eflujo de múltiples fármacos AcrB en Escherichia coli, que trabaja con TolC y AcrA, tiene un gran bolsillo de unión. Las estructuras cristalinas revelan un mecanismo rotativo de tres pasos para la exportación de fármacos a través de cambios ordenados de unión al sustrato.

Área de la Ciencia:

Microbiología Microbiología.
Biología Estructural Biología estructural.
La bioquímica es la bioquímica.

Sus antecedentes:

AcrB es un transportador de eflujo multidrug clave en Escherichia coli.
Funciona con TolC (canal de la membrana externa) y AcrA (proteína de fusión de la membrana).

Objetivo del estudio:

Para aclarar las bases estructurales del transporte multidrogas por AcrB.
Para entender el mecanismo de unión y exportación del sustrato.

Principales métodos:

Se utilizó la cristalografía de rayos X para determinar las estructuras de AcrB.
Se obtuvieron estructuras para AcrB solo y en complejo con sustratos de fármacos.

Principales resultados:

El complejo AcrB-droga reveló tres protómeros en distintos estados funcionales del ciclo de transporte.
Los sustratos se ubicaron en el dominio periplásmico dentro de un gran bolsillo de unión aromático que permite la unión en múltiples sitios.
Las estructuras cristalinas capturaron diferentes estados conformacionales del ciclo de transporte.

Conclusiones:

AcrB utiliza un mecanismo de rotación funcional para la exportación de drogas.
La unión y liberación del sustrato implican cambios conformacionales ordenados dentro del transportador.

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