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Un cambio conformacional a gran escala combina el reclutamiento de la membrana con la unión de la carga en el

Lauren P Jackson¹, Bernard T Kelly, Airlie J McCoy

¹Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.

|July 7, 2010

Resumen

El complejo de adaptadores AP2 sufre un cambio de conformación, desbloqueando los sitios de unión de carga. Este cambio estructural facilita el AP2

Área de la Ciencia:

Biología celular Biología celular.
Biología Molecular Biología Molecular
La bioquímica es la bioquímica.

Sus antecedentes:

El complejo adaptador AP2 es crucial para la endocitosis mediada por clatrina.
AP2 conecta la carga transmembrana con el andamio de clatrina a través de las membranas que contienen PtdIns4,5P(2).
En su forma citosólica, los sitios de unión de carga de AP2 están bloqueados por la subunidad beta2.

Objetivo del estudio:

Para aclarar el mecanismo estructural de la activación de AP2.
Para entender cómo AP2 transiciones de un "bloqueado" a un estado "abierto" para la carga de enlace.
Para investigar el papel de PtdIns4,5P(2) en la endocitosis mediada por AP2.

Principales métodos:

Se utilizó la cristalografía de proteínas para determinar la estructura de AP2.
Se emplearon técnicas biofísicas para estudiar las interacciones de AP2-membrana.
Se analizaron los cambios de conformación en las subunidades AP2.

Principales resultados:

AP2 sufre un cambio conformacional significativo, reubicando el dominio C-terminal de mu2 (C-mu2).
Esta reorganización desbloquea los sitios de unión de motivos endocíticos YxxPhi y [ED]xxxL[LI].
Los cuatro sitios de unión de PtdIns4,5P(2) y dos sitios de unión de carga se convierten en coplanares.
La interacción de AP2 con las membranas que contienen PtdIns4,5P(2) impulsa la unión de carga endocítica.

Conclusiones:

La flexibilidad conformacional de AP2 es esencial para su función en la endocitosis.
La unión simultánea a PtdIns4,5P(2) y a los motivos de carga es facilitada por la disposición coplanar de los sitios de unión.
La interacción de la membrana con PtdIns4,5P(2) es el principal motor para el reclutamiento de carga endocítica de AP2.

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