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Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
Published on: May 19, 2009
Mecanismo molecular de la unión de ATP y la activación del canal iónico en los receptores P2X
Motoyuki Hattori1, Eric Gouaux
1Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Nature
|April 27, 2012
Resumen
Los investigadores revelaron la estructura de los receptores P2X4 del pez cebra, detallando el sitio de unión al ATP y el poro del canal iónico abierto. Esto proporciona información crucial sobre los mecanismos de encierro de canales iónicos dependientes de ATP para el desarrollo de fármacos.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- La neurociencia es la neurociencia.
Sus antecedentes:
- Los receptores P2X son canales iónicos trímero ATP-gated cruciales para varios procesos fisiológicos.
- Comprender su estructura, particularmente el sitio de unión al ATP y el mecanismo de enlace, es vital para la farmacología.
Objetivo del estudio:
- Para determinar la estructura tridimensional del receptor P2X4 del pez cebra.
- Para dilucidar el mecanismo estructural de las compuertas de los canales iónicos dependientes de ATP.
- Para caracterizar la arquitectura de los poros del canal iónico abierto.
Principales métodos:
- Se utilizó cristalografía de rayos X para obtener estructuras del receptor P2X4 del pez cebra.
- Se determinaron estructuras tanto para el receptor apo como para el receptor en complejo con ATP.
Principales resultados:
- La estructura cristalina del receptor P2X4 del pez cebra en complejo con ATP reveló un nuevo motivo de unión al ATP y un poro de canal iónico abierto.
- La unión de ATP induce cambios conformacionales, incluido el cierre de hendiduras y la expansión radial del vestíbulo extracelular.
- La apertura del poro del canal iónico está acoplada a la ampliación del vestíbulo a través de la expansión de la hélice transmembrana.
Conclusiones:
- El estudio proporciona los primeros conocimientos estructurales sobre el sitio de unión al ATP y el poro abierto del canal iónico de los receptores P2X4.
- Los hallazgos esclarecen el mecanismo del encierro de los canales iónicos dependientes de ATP.
- Esta información estructural facilitará el desarrollo de nuevos agentes farmacológicos dirigidos a los receptores P2X.
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