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Conocimientos estructurales sobre el mecanismo de detección de redox del regulador de tipo MarR AbfR
Guijie Liu1,2, Xing Liu1,3, Hongjiao Xu1,2
1Laboratory of Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
Journal of the American Chemical Society
|January 15, 2017
Resumen
La regulación del estrés oxidativo por Staphylococcus epidermidis AbfR incluye modificaciones de la cisteína. Los enlaces de disulfuro reversibles, no la sobreoxidación, inhiben la unión al ADN, revelando nuevos mecanismos de detección de redox.
Área de la Ciencia:
- Microbiología
- Biología estructural
- La bioquímica
Sus antecedentes:
- AbfR es un regulador transcripcional maestro de la familia MarR que detecta la oxidación-reducción en el Staphylococcus epidermidis.
- Desempeña un papel crítico en las respuestas al estrés oxidativo y la regulación de la virulencia.
Objetivo del estudio:
- Para aclarar el mecanismo de unión al ADN de AbfR en varios estados de oxidación.
- Para comprender la base estructural de la regulación redox de AbfR.
Principales métodos:
- Cristalografía de rayos X del complejo de AbfR/ADN reducido, AbfR/ADN sobreoxidado y dimero de AbfR con enlaces cruzados de 2-disulfuro.
- Los análisis bioquímicos.
Principales resultados:
- La modificación de disulfuro reversible, a diferencia de la sobreoxidación irreversible, deteriora significativamente la capacidad de unión al ADN de AbfR.
- Tanto el 1-disulfuro como el 2-disulfuro enlazados con los dimeros AbfR son biológicamente pertinentes.
- La AbfR sobreoxidada retiene la unión al ADN pero no es biológicamente significativa.
- El enlace cruzado de 1-disulfuro debilita la unión al ADN; el enlace cruzado de 2-disulfuro da como resultado una conformación abierta incompatible con la unión al ADN.
Conclusiones:
- La regulación redox de AbfR implica características nuevas, incluido el impacto diferencial de los enlaces disulfuro frente a la sobreoxidación en la unión al ADN.
- La química de oxidación concisa de la cisteína permite una detección y respuesta eficientes al estrés oxidativo en AbfR.
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