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Los estados de reposo y activo del complejo ERK2:HePTP
Dana M Francis1, Bartosz Różycki, Antoni Tortajada
1Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island 02912, USA.
Journal of the American Chemical Society
|October 12, 2011
Resumen
La tirosina fosfatasa hematopoyética (HePTP) regula la activación de las células T mediante la desfosforilación de la quinasa regulada por la señal extracelular 2 (ERK2). Este estudio revela cambios estructurales en los complejos ERK2:HePTP, ofreciendo información sobre los estados activos.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
Sus antecedentes:
- La actividad de la quinasa regulada por la señal extracelular 2 (ERK2) está fuertemente regulada por las fosfatasas.
- La tirosina fosfatasa hematopoyética (HePTP) regula negativamente la activación de las células T a través de la desfosforilación de ERK2.
- Existen datos estructurales limitados para estos complejos enzimáticos críticos.
Objetivo del estudio:
- Caracterizar estructuralmente los estados de reposo y activo de los complejos ERK2:HePTP.
- Proporcionar los primeros conocimientos estructurales sobre un complejo activo de proteína quinasa activada por mitógeno (MAPK).
Principales métodos:
- Diseminación de rayos X de ángulo pequeño (SAXS).
- Refinamiento del conjunto de EROS.
Principales resultados:
- El complejo ERK2:HePTP en estado de reposo exhibe una conformación dinámica y extendida.
- El complejo ERK2:HePTP en estado activo adopta una estructura compacta y ordenada.
- En la solución se producen cambios estructurales dinámicos significativos.
Conclusiones:
- Los complejos ERK2:HePTP experimentan cambios conformacionales sustanciales entre los estados de reposo y activo.
- Este estudio proporciona nuevos conocimientos estructurales sobre los complejos activos de MAPK.
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