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Conocimientos estructurales y mecanicistas sobre la iniciación mediada por STIM1 de la entrada de calcio operado en
Peter B Stathopulos1, Le Zheng, Guang-Yao Li
1Division of Signaling Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto Medical Discovery Tower, MaRS Centre, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
Cell
|October 16, 2008
Resumen
La molécula de interacción estroma-1 (STIM1) regula la entrada de calcio. Su región EF-SAM sensible al Ca2+ es la región EF-SAM.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La molécula de interacción del estromal-1 (STIM1) es un regulador clave de la entrada de calcio operado por almacenamiento (SOCE).
- La activación de STIM1 se desencadena por la reducción de los niveles de calcio dentro de las reservas intracelulares.
Objetivo del estudio:
- Para determinar la estructura atómica de la región EF-SAM con detección de Ca2+ de STIM1.
- Para dilucidar los mecanismos moleculares subyacentes a la iniciación SOCE mediada por STIM1.
Principales métodos:
- Cristalografía de rayos X para determinar la estructura atómica del dominio STIM1 EF-SAM.
- Mutagénesis dirigida al sitio para investigar el papel de residuos y dominios específicos.
- Ensayos basados en células en células de mamíferos para evaluar la función STIM1 y la actividad SOCE.
Principales resultados:
- La estructura atómica de la región STIM1 EF-SAM reveló un par de motivos de manos EF que interactúan con el dominio SAM.
- Las mutaciones que interrumpieron las interacciones de la mano EF o el dominio SAM desestabilizaron la entidad EF-SAM, afectando la sensibilidad al Ca2+ y la oligomerización.
- Las mutaciones de desestabilización en la formación de punctae inducida por STIM1 de longitud completa y la activación SOCE independiente de Ca2+ en las células.
Conclusiones:
- El estado plegado / desplegado de la región STIM1 EF-SAM es crítico para regular SOCE.
- Las percepciones estructurales a nivel atómico explican la base molecular de la iniciación SOCE mediada por STIM1.
- Las interacciones del par EF-mano y el dominio SAM son esenciales para la sensibilidad y la función de Ca2+ de STIM1.
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