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La estructura cristalina del ectodominio receptor del factor de crecimiento de los fibroblastos unido al ligando y a
L Pellegrini1, D F Burke, F von Delft
1Department of Biochemistry, University of Cambridge, UK. luca@cryst.bioc.cam.ac.uk
Nature
|November 9, 2000
Resumen
Este estudio revela la estructura cristalina de un complejo de señalización del factor de crecimiento de los fibroblastos (FGF). La estructura aclara el papel esencial del sulfato de heparano en la mediación de las interacciones del FGF y los receptores para la señalización celular.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
Sus antecedentes:
- Los factores de crecimiento de los fibroblastos (FGF) son proteínas cruciales involucradas en diversos procesos fisiológicos y patológicos.
- La señalización del FGF se basa en un complejo ternario de FGF, su receptor tirosina quinasa (FGFR) y proteoglicano de sulfato de heparan.
- La arquitectura molecular precisa de este complejo de señalización sigue siendo en gran medida desconocida.
Objetivo del estudio:
- Para dilucidar la arquitectura molecular del complejo de señalización FGF.
- Para determinar la estructura cristalina del ectodominio FGFR2 unido al FGF1 y a la heparina.
- Proporcionar una base estructural para el papel del sulfato de heparan en la transducción de señales FGF.
Principales métodos:
- Se empleó cristalografía de rayos X para determinar la estructura del complejo ternario.
- El complejo consistía en el ectodominio FGFR2, FGF1 y un decasacárido de heparina.
- El análisis estructural se centró en las interacciones dentro del complejo de señalización ensamblado.
Principales resultados:
- La estructura cristalina reveló una forma dimérica del ectodominio FGFR2 inducido por la unión de FGF1 y heparina.
- Una molécula central de heparina une dos ligandos FGF1, que a su vez unen dos cadenas de receptores.
- La unión de la heparina fue asimétrica, interactuando con ambas moléculas de FGF1 pero solo con una cadena de receptores.
Conclusiones:
- La estructura determinada proporciona la primera visión molecular detallada del complejo ternario FGF-FGFR-sulfato de heparano.
- Esta estructura pone de relieve el papel crítico del sulfato de heparan como un andamio molecular esencial para la señalización del FGF.
- Los hallazgos ofrecen una base estructural para comprender las actividades biológicas mediadas por el FGF.
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