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Estructura, inhibición y regulación del canal de dos poros TPC1 de la Arabidopsis thaliana
Alexander F Kintzer1, Robert M Stroud1
1Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.
Nature
|March 11, 2016
Resumen
La estructura cristalina de los canales de dos poros de las plantas (TPC) revela cómo controlan el flujo de iones y se regulan. Esto proporciona información sobre su función y posibles objetivos farmacológicos para enfermedades como la infección por el virus Ebola.
Área de la Ciencia:
- Biología estructural
- Fisiología molecular
- Ciencias de las plantas
Sus antecedentes:
- Los canales de dos poros (TPC) son canales iónicos eucariotas que regulan el flujo iónico, el pH y el tráfico en los compartimentos endolisomales.
- Las TPC son cruciales para los procesos celulares y están implicadas en infecciones virales, incluido el virus del Ébola.
Objetivo del estudio:
- Para determinar la estructura cristalina de la especie Arabidopsis thaliana TPC1.
- Elucidar los mecanismos de permeación iónica, activación de canales y regulación por voltaje, iones y fosforilación.
Principales métodos:
- Cristalografía de rayos X con una resolución de 2,87 Å.
- Análisis estructural para identificar los dominios de detección de tensión y los sitios reguladores.
Principales resultados:
- La estructura cristalina de TPC1 revela características clave para la permeación y activación de iones.
- Se identificaron sitios de fosforilación que modulan alostericamente la activación del calcio.
- Se caracterizó un dominio sensible a la tensión (VSD2), que muestra una conformación distinta.
- Se demostró que el farmacóforo trans-Ned-19 se une alostéricamente, sujetando los dominios de los poros a la VSD2.
Conclusiones:
- La estructura TPC1 proporciona una base para comprender la función y la regulación del canal TPC.
- Los conocimientos estructurales pueden guiar el desarrollo de terapias dirigidas a las TPC para infecciones virales y otras enfermedades.
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