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La estructura de un complejo p110alpha/p85alpha humano aclara los efectos de las mutaciones oncogénicas PI3Kalpha
Chuan-Hsiang Huang1, Diana Mandelker, Oleg Schmidt-Kittler
1Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Science (New York, N.Y.)
|December 15, 2007
Resumen
El gen PIK3CA.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
Sus antecedentes:
- PIK3CA es un oncogén con frecuencia mutado en tumores humanos.
- Se codifica p110alpha, la subunidad catalítica del fosfatidilinositol 3-kinasa alfa (PI3Kalpha).
- p85alpha se requiere para la actividad enzimática de PI3Kalpha.
Objetivo del estudio:
- Para determinar la estructura de resolución de 3.0 angstrom del complejo p110alpha/p85alpha.
- Comprender las bases estructurales de la regulación de PI3Kalpha y las mutaciones oncogénicas.
Principales métodos:
- Cristalografía de rayos X para determinar la estructura compleja.
Principales resultados:
- La estructura revela que las mutaciones a menudo ocurren en las interfaces entre p110alpha y p85alpha.
- Las mutaciones pueden interrumpir la regulación mediada por p85alfa de la actividad de la quinasa.
- Otras mutaciones afectan la actividad catalítica intrínseca del dominio de la quinasa.
Conclusiones:
- La estructura proporciona información sobre la función de PI3Kalpha.
- Sugiere mecanismos para las mutaciones oncogénicas en PIK3CA y p85alpha.
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