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El mecanismo de liberación de sodio y sustrato del bolsillo de unión de vSGLT
Akira Watanabe1, Seungho Choe, Vincent Chaptal
1Department of Physiology, University of California, Los Angeles, Los Angeles, California 90095-1759, USA.
Nature
|December 7, 2010
Resumen
Los transportadores de sodio / galactosa (vSGLT) utilizan la liberación de sodio para desencadenar cambios conformacionales, asegurando la liberación oportuna de iones y sustratos. Una vía alostérica enlaza la unión de sodio, hélice 1 y la unión de sustrato para el transporte acoplado.
Área de la Ciencia:
- Biología estructural Biología estructural.
- La bioquímica es la bioquímica.
- La biofísica es la biofísica.
Sus antecedentes:
- Los transportadores activos secundarios utilizan gradientes iónicos para el transporte del sustrato.
- Las proteínas de co-transporte de membrana con un motivo de repetición invertido de cinco hélices son una clase importante de transportadores.
- El mecanismo de acoplamiento del transporte de iones y sustratos en estas proteínas sigue sin estar claro.
Objetivo del estudio:
- Para dilucidar el mecanismo de acoplamiento de iones y sustratos en el transportador de sodio/galactosa de Vibrio parahaemolyticus (vSGLT).
- Para investigar las bases estructurales y dinámicas de la función vSGLT.
Principales métodos:
- Cristalografía de rayos X para determinar la conformación de apertura hacia adentro de vSGLT a una resolución de 2.7 Å.
- Simulaciones de dinámica molecular para analizar la dinámica de las proteínas y los cambios conformacionales.
- Caracterización bioquímica para evaluar la función del transportador.
Principales resultados:
- La salida de sodio induce una reorientación de la hélice transmembrana 1, abriendo una puerta interior para la liberación del sustrato.
- La liberación de sodio desencadena pequeños movimientos de cuerpo rígido en haces helicoidales, asegurando la liberación coordinada de iones y sustratos.
- Se identificó una vía alostérica que conecta los sitios de unión al sodio, la hélice transmembrana 1 y el sitio de unión al sustrato, crucial para el acoplamiento de transporte conjunto.
Conclusiones:
- El estudio revela un mecanismo detallado para el co-transporte de sodio-galactosa en vSGLT, iniciado por la liberación de sodio.
- Los cambios de conformación impulsados por la liberación de iones aseguran el momento preciso de la translocación del sustrato.
- La vía alostérica identificada es esencial para el acoplamiento funcional del transporte de iones y sustratos en esta clase de transportadores.
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