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Deriving the Time Course of Glutamate Clearance with a Deconvolution Analysis of Astrocytic Transporter Currents
Published on: August 7, 2013
Dinámica del transporte en un homólogo del transportador de glutamato
Nurunisa Akyuz1, Roger B Altman, Scott C Blanchard
1Department of Physiology and Biophysics, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10064, USA.
Nature
|June 25, 2013
Resumen
Los transportadores de glutamato se mueven a través de grandes cambios de dominio. Un paso clave implica que los dominios de transporte se desprenden de su andamio, precediendo el movimiento de transmembrana, que puede controlar la velocidad de transporte.
Área de la Ciencia:
- Bioquímica y Biología Molecular.
- La neurociencia es la neurociencia.
- Biología Estructural Biología estructural.
Sus antecedentes:
- Los transportadores de glutamato son proteínas vitales integrales de la membrana responsables de la captación de los neurotransmisores.
- Su función depende de los cambios conformacionales entre los estados orientados hacia afuera y hacia adentro.
- Los modelos anteriores proponían movimientos transmembranares de dominios de transporte discretos dentro de un andamio trímero.
Objetivo del estudio:
- Para visualizar directamente los movimientos del dominio de transporte a gran escala en los transportadores de glutamato.
- Para dilucidar el mecanismo de las transiciones conformacionales durante el transporte de neurotransmisores.
Principales métodos:
- Imágenes de transferencia de energía por resonancia de fluorescencia de una sola molécula (smFRET) empleadas.
- Estudió un homólogo bacteriano de transportadores de glutamato para observar la dinámica del dominio.
Principales resultados:
- Se observaron directamente movimientos a gran escala de los dominios de transporte.
- Los dominios de transporte exhiben períodos de quiescencia que se alternan con transiciones rápidas, similares al estallido del canal iónico.
- Se identificó un desprendimiento lento y espontáneo de los dominios de transporte cargados de sustrato del andamio trímero que precede a los movimientos transmembranares.
Conclusiones:
- El modo dinámico en los transportadores de glutamato se inicia por la separación del dominio de transporte del andamio.
- Este paso de desalojo es significativamente más lento que los movimientos subsecuentes de transmembrana.
- El mecanismo de separación de dominio puede ser el paso limitante de velocidad en el ciclo del transportador de glutamato.
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