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Bases estructurales de la transinhibición en un transportador ABC de molibdato y tungsteno
Sabina Gerber1, Mireia Comellas-Bigler, Birke A Goetz
1Institute of Molecular Biology and Biophysics, ETH Zürich, HPK D14.3, 8093 Zürich, Switzerland.
Science (New York, N.Y.)
|May 31, 2008
Resumen
Los investigadores revelaron la base estructural de la transinhibición en los transportadores de membrana. La unión de molibdato/tungstato a un transportador ABC (ModBC) lo encierra en un estado orientado hacia adentro, impidiendo el transporte del sustrato.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Las proteínas de transporte de membrana son cruciales para la función celular.
- La transinhibición, donde los sustratos inhiben la rotación del transportador, carece de una comprensión estructural clara.
Objetivo del estudio:
- Para dilucidar las bases estructurales de la transinibición en los transportadores de molibdato/tungstato ABC.
- Comprender cómo la unión del sustrato afecta la conformación y la actividad del transportador.
Principales métodos:
- Se utilizó cristalografía de rayos X para determinar la estructura del transportador ModBC.
- Análisis de la estructura cristalina en un estado transinhibido.
Principales resultados:
- Se determinó la estructura cristalina del transportador de Methanosarcina acetivorans ModBC en un estado trans-inhibido.
- Se identificaron bolsas de unión de oxyaniones en la interfaz de los dominios reguladores en las subunidades de unión de nucleótidos.
- La unión de molibdato o tungstato impide la actividad de la ATPasa y bloquea el transportador en una conformación orientada hacia adentro.
Conclusiones:
- La unión al sustrato (molibdato/tungstato) induce un efecto alostérico, inhibiendo la actividad de la ATPasa.
- Esta inhibición impide que el transportador alterne entre estados orientados hacia adentro y hacia afuera, bloqueando así el transporte.
- El estudio proporciona un mecanismo estructural para la transinhibición en los transportadores ABC.
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