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Las uniones estrechas. uniones estrechas. Conocimiento estructural sobre el desmontaje de las uniones estrechas por
Yasunori Saitoh1, Hiroshi Suzuki2, Kazutoshi Tani2
1Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. Department of Basic Medical Science, Graduate School of Pharmaceutical Science, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Science (New York, N.Y.)
|February 14, 2015
Resumen
La enterotoxina de Clostridium perfringens (C-CPE) se une a la claudina-19, interrumpiendo las uniones cerradas. El análisis estructural revela que la interacción C-CPE desplaza una hélice clave, lo que explica el desmontaje de la TJ y el aumento de la permeabilidad.
Área de la Ciencia:
- Biología molecular La biología molecular.
- Biología estructural Biología estructural.
- Biología celular Biología celular.
Sus antecedentes:
- La enterotoxina de Clostridium perfringens (C-CPE) se dirige a las claudinas, lo que lleva al desmontaje de la unión estrecha (TJ) y al aumento de la permeabilidad epitelial.
- Comprender las interacciones moleculares entre el C-CPE y las claudinas es crucial para elucidar los mecanismos patógenos del C-CPE.
Objetivo del estudio:
- Determinar la estructura de alta resolución del complejo formado entre la claudina-19 de mamíferos y C-CPE.
- Para aclarar la base estructural para la interrupción mediada por C-CPE de las uniones estrechas.
Principales métodos:
- Se utilizó cristalografía de rayos X para obtener la estructura del complejo claudin-19/C-CPE a una resolución de 3,7 Å.
Principales resultados:
- La estructura revela extensas interacciones hidrofóbicas e hidrofílicas entre C-CPE y los segmentos extracelulares de la claudina-19.
- Una hélice extracelular crítica, esencial para el ensamblaje de la hebra TJ en las claudinas, estaba ausente en la estructura del complejo claudin-19/C-CPE.
- Esta ausencia sugiere que la unión C-CPE desplaza esta hélice, lo que podría conducir al desmontaje de la TJ.
Conclusiones:
- La región C-terminal de C-CPE interactúa con la claudina-19, alterando la estructura de la TJ.
- El desplazamiento de una hélice extracelular crítica por la unión de C-CPE es un mecanismo probable para el desmontaje de la unión apretada inducido por C-CPE y el aumento de la permeabilidad paracelular.
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