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Estructura cristalina del sensor de estrés DegS: Cómo un dominio PDZ reconoce la proteína mal plegada y activa una

Corinna Wilken¹, Karina Kitzing, Robert Kurzbauer

¹Institute for Molecular Pathology (IMP), Dr. Bohrgasse 7, A-1030 Vienna, Austria.

|May 13, 2004

Resumen

La proteasa DegS, esencial para la respuesta bacteriana al estrés, se activa mediante péptidos de señalización de estrés que se unen a su dominio PDZ. Esta unión desencadena cambios conformacionales, lo que permite la función de la proteasa y la activación reversible.

Área de la Ciencia:

Microbiología Microbiología.
Biología Estructural Biología estructural.
La bioquímica es la bioquímica.

Sus antecedentes:

Las bacterias gramnegativas emplean la vía sigmaE para manejar las proteínas mal plegadas en la envoltura celular.
La proteasa DegS inicia una cascada proteolítica crucial para la activación de sigmaE mediante la escisión del factor antisigma RseA.

Objetivo del estudio:

Para dilucidar los mecanismos estructurales que subyacen a la activación de la proteasa DegS por los péptidos de señalización de estrés.
Investigar el papel del dominio PDZ en la detección del estrés periplásmico y la regulación de la actividad de la proteasa.

Principales métodos:

Se utilizó la cristalografía de rayos X para determinar las estructuras de tres estados distintos de E. coli DegS.
Análisis de DegS solo, DegS unido a péptidos activadores y estados híbridos activo/inactivo.

Principales resultados:

DegS existe en una forma catalíticamente inactiva en ausencia de activadores.
La unión de los péptidos de señalización de estrés con el dominio PDZ induce cambios conformacionales que activan DegS.
El análisis estructural reveló un mecanismo de activación reversible, incluyendo un estado híbrido activo/inactivo.

Conclusiones:

DegS funciona como un sensor de estrés periplásmico, traduciendo la unión del péptido en la activación de la proteasa.
Los dominios PDZ juegan un nuevo papel regulador en la activación de la proteasa.
Se ha identificado un nuevo mecanismo para la activación reversible de la proteasa en respuesta al estrés celular.

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