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Activación de proteínas con resolución en el tiempo por decadencia proximal en sistemas vivos

Jie Wang^1,2, Yuan Liu¹, Yanjun Liu¹

¹Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.

|May 10, 2019

Resumen

Los investigadores desarrollaron un nuevo método, CAGE-prox, para controlar con precisión la actividad de las proteínas en las células y los animales. Esta técnica permite la activación de las proteínas con resolución temporal, avanzando en el estudio de los procesos biológicos dinámicos.

Área de la Ciencia:

Biología molecular
La bioquímica
La genética

Sus antecedentes:

La comprensión de los procesos celulares dinámicos requiere un control preciso sobre la actividad de las proteínas.
Los métodos existentes para la activación de proteínas temporales tienen limitaciones.

Objetivo del estudio:

Desarrollar una estrategia universal, computacionalmente asistida y genéticamente codificada para el control selectivo y temporal de la actividad de las proteínas.
Permitir estudios de ganancia de función con resolución temporal en sistemas vivos.

Principales métodos:

Desarrolló la estrategia CAGE-prox (decadencia proximal asistida por computación y codificada genéticamente).
Aminoácidos foto-enjaulados genéticamente incorporados cerca de los sitios funcionales de las proteínas.
Diseño computacional utilizado para el bloqueo de la actividad de proteínas temporales y la reactivación rápida inducida por la luz.

Principales resultados:

Se ha demostrado una amplia aplicabilidad en diversas familias de proteínas.
Habilitado la sintonía ortogonal de la señalización celular y las respuestas inmunes.
Facilitó el perfilamiento temporal de sustratos proteolíticos y el desarrollo de una terapia pro-droga basada en proteínas.

Conclusiones:

CAGE-prox ofrece una herramienta poderosa para estudios precisos de ganancia de función con resolución temporal.
El método avanza en la comprensión de los procesos biológicos dinámicos en células vivas y ratones.
Abre el camino para nuevas estrategias terapéuticas y vías de investigación biológica.

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