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Los ciclos de plegamiento de proteínas fútiles en la ER son terminados por la vía de O-mannosilación de proteínas

Chengchao Xu¹, Songyu Wang, Guillaume Thibault

¹Temasek Life Sciences Laboratory, National University of Singapore, Singapore.

Science (New York, N.Y.)

|May 25, 2013

Resumen

El plegamiento de proteínas en el retículo endoplasmático (ER) puede ser terminado por O-manosilación, una modificación del azúcar. Este proceso evita que las proteínas mal plegadas consuman recursos celulares y promueve su degradación.

Área de la Ciencia:

La bioquímica es la bioquímica.
Biología celular Biología celular.
Biología Molecular Biología Molecular

Sus antecedentes:

Los polipéptidos recién sintetizados requieren acompañantes de proteínas para el plegado y el ensamblaje adecuados.
Los intentos fallidos de plegamiento conducen a la degradación del sustrato, pero el ciclo prolongado en el retículo endoplasmático (ER) es perjudicial.
El estrés ER puede surgir de proteínas mal plegadas acumuladas, que consumen recursos celulares y aumentan las especies reactivas de oxígeno.

Objetivo del estudio:

Investigar los mecanismos por los cuales los intentos fallidos de plegamiento de proteínas se terminan en la ER.
Para identificar procesos celulares específicos que eviten el ciclo prolongado del sustrato y la degradación.
Para aclarar el papel de las modificaciones post-traduccionales en el control de calidad del plegamiento de proteínas.

Principales métodos:

Utilizó la levadura en ciernes como un organismo modelo.
Se emplean en ensayos de replegamiento de proteínas in vitro. ensayos de replegamiento de proteínas.
Investigó la función del complejo Pmt1/Pmt2 en la O-manosilación.
Se analizó la interacción entre los sustratos O-manosilados y el chaperón Kar2.

Principales resultados:

Se descubrió que la O-manosilación de proteínas desplegadas por el complejo Pmt1/Pmt2 pone fin a los intentos fallidos de plegamiento en la levadura en ciernes.
Se demostró que la O-manosilación incapacita irreversiblemente el potencial de plegamiento de las proteínas del sustrato.
Se demostró que la O-manosilación reduce el compromiso del sustrato con el chaperón Kar2, lo que facilita la eliminación de los ciclos de plegado.
Se confirmó que esta modificación evita el ciclo prolongado del sustrato, conservando así los recursos celulares.

Conclusiones:

La terminación del plegamiento de las proteínas se puede lograr a través de un evento de glicosilación covalente, específicamente O-manosilación.
La O-manosilación sirve como un mecanismo crítico de control de calidad en la ER, previniendo los efectos perjudiciales de los intentos prolongados de plegamiento de proteínas.
Este estudio revela un nuevo papel para la glicosilación en la regulación de la homeostasis de las proteínas y la prevención del estrés celular.

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