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Estructura del complejo de canales de calcio Cav1.1 dependiente de la tensión

Jianping Wu¹, Zhen Yan¹, Zhangqiang Li¹

¹State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China. Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.

Science (New York, N.Y.)

|December 19, 2015

Resumen

Determinamos la estructura del canal de calcio controlado por la tensión Ca ((v) 1.1, crucial para la contracción del músculo esquelético. Esto revela la disposición de sus subunidades, ofreciendo información sobre la función del canal y las enfermedades relacionadas.

Área de la Ciencia:

La biofísica
Biología molecular
Biología estructural

Sus antecedentes:

El canal de calcio controlado por voltaje Ca ((v) 1.1 media el acoplamiento excitación-contracción en los músculos esqueléticos.
El complejo Ca (v) 1.1 comprende una subunidad α1 formadora de poros y subunidades auxiliares α2δ, β y γ.

Objetivo del estudio:

Determinar la estructura de alta resolución del complejo Ca(v) 1.1 del conejo.
Para aclarar la organización arquitectónica y las interacciones de las subunidades dentro del canal Ca (v) 1.1.

Principales métodos:

Microscopía criolectrónica de una sola partícula (cryo-EM).

Principales resultados:

Las cuatro repeticiones homólogas de la subunidad α1 están dispuestas en el sentido de las agujas del reloj en la vista extracelular.
La subunidad γ interactúa con VSD, la subunidad β está cerca de VSD, y la subunidad α2 se une a los bucles extracelulares de repeticiones I-III.
La estructura revela la arquitectura detallada del complejo Ca ((v) 1.1).

Conclusiones:

La estructura determinada representa un prototipo de canal de Ca ((v) eucariota.
Este marco estructural ayuda a comprender la función de Ca (v) 1.1 y los mecanismos de enfermedad de los canales de Ca (v) y Na (v).

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