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Mecanismo de apertura y cierre de canales en los receptores de glutamato del subtipo AMPA
Edward C Twomey1,2, Maria V Yelshanskaya1, Robert A Grassucci1,3
1Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, New York 10032, USA.
Nature
|July 25, 2017
Resumen
Este estudio revela el mecanismo similar al iris de la apertura del canal iónico en los receptores de ácido α-amino-3-hidroxi-5-metil-4-isoxazol propiónico (AMPA). La comprensión de la entrada del receptor AMPA es crucial para la investigación de enfermedades neurológicas.
Área de la Ciencia:
- La neurociencia
- Biología estructural
- La bioquímica
Sus antecedentes:
- Los receptores AMPA median la neurotransmisión excitatoria rápida en el sistema nervioso central.
- La desregulación de la señalización del receptor AMPA está implicada en varias enfermedades neurológicas.
- Los receptores AMPA son críticos para la fuerza y la función sináptica.
Objetivo del estudio:
- Para aclarar la base estructural de la puerta del canal de iones del receptor AMPA.
- Determinar el mecanismo de apertura de los canales en los estados apo, antagonista y agonista.
- Proporcionar un marco para la comprensión del receptor de glutamato ionotrópico.
Principales métodos:
- Se utilizó la criomicroscopia electrónica (crio-EM) para resolver estructuras de alta resolución.
- Se determinaron las estructuras de los complejos de subunidades auxiliares de los receptores de AMPA.
- Se analizaron los cambios conformacionales durante la activación y la desensibilización.
Principales resultados:
- Se aclaró el mecanismo de apertura del canal iónico similar al iris.
- Los bucles M2 forman el filtro de selectividad del canal iónico.
- Se identificaron cambios conformacionales en el receptor de AMPA durante la entrada.
Conclusiones:
- El estudio proporciona información a nivel atómico sobre la función del receptor AMPA.
- Los hallazgos ofrecen un marco estructural para la comprensión del receptor de glutamato ionotrópico.
- Esta investigación es vital para el desarrollo de estrategias terapéuticas para los trastornos neurológicos.
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