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Base molecular para el enlace aniónico diferencial y el acoplamiento de protones en el intercambiador ClC-ec1

Tao Jiang¹, Wei Han¹, Merritt Maduke²

¹Department of Biochemistry, Center for Biophysics and Computational Biology, and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Champaign, Illinois 61801, United States.

Journal of the American Chemical Society

|February 17, 2016

Resumen

Los transportadores de cloruro/protón (Cl/H+) utilizan distintos mecanismos de unión de aniones para regular el transporte de protones. Diferentes aniones, como el fluoruro o el nitrato, interrumpen los cables de agua esenciales para la transferencia de protones, afectando la función del transportador.

Área de la Ciencia:

Biología molecular
La bioquímica
Transporte por membrana

Sus antecedentes:

Los transportadores de cloruro/protón (Cl/H+) son proteínas de membrana cruciales que facilitan el intercambio iónico.
La superfamilia CLC media el transporte acoplado de Cl y H+, pero el mecanismo exacto, especialmente el acoplamiento H+ dependiente de aniones, sigue sin estar claro.
Estudios anteriores destacaron la importancia de la unión de Cl en el sitio central de unión de aniones (Scen) para el transporte de H+ en el ClC-ec1 bacteriano.

Objetivo del estudio:

Aclarar la base estructural de la unión aniónica y su impacto en el transporte de H+ en el transportador ClC-ec1.
Investigar cómo los diferentes aniones (Cl, F, NO3, SCN) interactúan con el sitio Scen e influyen en la formación de cables de agua.

Principales métodos:

Análisis estructural de ClC-ec1 en complejo con varios aniones (Cl, F, NO3, SCN).
Investigación de la coordinación de la unión aniónica y los estados de hidratación en el sitio de la escena.
Evaluación de la formación de cables de agua transitorios necesarios para la transferencia de protones entre los sitios GluiN y GluiX.

Principales resultados:

Se observaron modos de unión y patrones de hidratación distintos para Cl, F, NO3 y SCN en el sitio de Scen.
La capacidad de ClC-ec1 para formar cables de agua continuos varió significativamente con diferentes aniones.
Mientras que Cl facilitaba los cables de agua continuos, F y NO3 formaban pseudo-cables de agua, y SCN abolió completamente los cables de agua.

Conclusiones:

La unión de aniones en el sitio de la escena dicta la formación de cables de agua cruciales para el transporte de protones.
La unión diferencial de aniones proporciona un mecanismo estructural que explica el acoplamiento variable de H+ observado para diferentes aniones en los transportadores CLC.
Estos hallazgos ofrecen información a nivel atómico sobre el desacoplamiento del transporte de H+ de los aniones no clorados.

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