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La activación de la toxina Tc requiere el despliegue y repliegue de una hélice β

  • 0Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
Nature +

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21 de septiembre de 2018

|

21 de septiembre de 2018

Ver abstracta en PubMed

Resumen

Este resumen es generado por máquina.

Las proteínas tóxicas (T) utilizan un mecanismo similar a una jeringa para inyectar enzimas en las células huésped. Este estudio revela cómo el ensamblaje de la proteína T, que implica el despliegue y el repliegue, activa la entrega de toxinas en el canal de translocación.

Área De La Ciencia

  • Biología molecular
  • Biología estructural
  • Microbiología

Sus Antecedentes

  • Las proteínas tóxicas (T) son factores de virulencia secretados en las células huésped a través de un aparato parecido a una jeringa.
  • Las proteínas T consisten en tres subunidades: TcA (canal de translocación) y TcB-TcC (capullo que protege la enzima tóxica).
  • La unión del capullo al canal inicia la liberación de enzimas y la translocación.

Objetivo Del Estudio

  • Para aclarar el mecanismo a nivel atómico de ensamblaje y activación de la proteína T.
  • Para entender los reordenamientos estructurales involucrados en la translocación de toxinas.

Principales Métodos

  • Cristalografía de rayos X
  • Microscopía criolectrónica
  • Ensayos bioquímicos

Principales Resultados

  • Las subunidades del capullo (TcC) se despliegan y vuelven a plegarse completamente al unirse al canal TcA.
  • La presencia de enzimas tóxicas es crucial para la unión de alta afinidad entre el capullo y el TcA.
  • La enzima navega por una constricción cargada negativamente dentro del capullo, facilitando la extrusión terminal C en el canal de translocación.

Conclusiones

  • El ensamblaje de las subunidades de la proteína T implica cambios conformacionales significativos, incluido el desdoblamiento y el repliegue de la proteína.
  • La enzima tóxica actúa como un componente clave en el proceso de activación y unión.
  • Este mecanismo destaca una nueva estrategia para la translocación de proteínas a través de las membranas celulares.

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