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Plegado y despliegue de un receptor transmembrana totalmente sintético para la transducción de señales ON/OFF

Shihao Pang¹, Jiawei Liu¹, Tianlong Li²

¹Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China.

Journal of the American Chemical Society

|September 12, 2023

Resumen

Los investigadores desarrollaron un nuevo receptor artificial para la transducción de señales controlable. Este sistema utiliza cambios de conformación del pliegue, desencadenados por iones de zinc, para cambiar las vías de señalización biológica de manera reversible.

Área de la Ciencia:

Bioquímica y Biología Molecular
Biología sintética
Ciencias de los materiales

Sus antecedentes:

La transducción de señales en los organismos se basa en cambios conformacionales en los receptores de proteínas transmembrana.
El desarrollo de modelos artificiales para la transducción de señales a través de cambios conformacionales es un desafío.

Objetivo del estudio:

Diseñar y demostrar un nuevo receptor artificial para la transducción de señales controlable.
Para imitar la transmisión de señales biológicas utilizando cambios conformacionales artificiales.

Principales métodos:

Construyó un receptor artificial con un grupo de cabeza anclado en lípidos, una fracción de plegador transmembrana y un grupo de cola precatalizador.
Se inserta el receptor en una membrana lipídica.
Se utilizan iones de zinc (Zn2+) y ligandos competitivos para inducir y revertir cambios conformacionales.

Principales resultados:

Adición de foldamer inducido por Zn2+, que altera la conformación molecular y activa el grupo de cola del precatalizador.
Esta activación condujo a la transducción de la señal, logrando un estado "ON".
Un ligando competitivo invirtió el proceso, convirtiendo la transducción de la señal en "OFF".

Conclusiones:

El receptor artificial proporciona un nuevo modelo para la construcción de sistemas de transducción de señales controlables.
Las señales externas pueden activar y desactivar de forma reversible la catálisis intravesicular.
Demuestra el potencial de los sistemas basados en foldamer en biología sintética.

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