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Estructura del receptor de adhesión acoplado a Gq, ADGRL4

Qingchao Chen¹, Anastasiia Gusach¹, Aurora Diamante²

¹MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.

Nature communications

|December 30, 2025

Resumen

Los receptores acoplados a proteínas G de adhesión (aGPCR), como ADGRL4, son cruciales en el cáncer. Este estudio revela que ADGRL4 se acopla débilmente a la proteína Gq, ofreciendo nuevas dianas terapéuticas para cánceres intratables.

Área de la Ciencia:

Bioquímica
Biología Molecular
Biología Estructural

Sus antecedentes:

Los receptores acoplados a proteínas G de adhesión (aGPCR) son vitales para diversas funciones celulares, incluida la biología del cáncer.
ADGRL4 está sobreexpresado en tumores y se implica en la patogénesis, presentando una diana terapéutica potencial para cánceres como el glioblastoma.

Objetivo del estudio:

Investigar el acoplamiento a G proteína y la estructura de ADGRL4.
Comprender los mecanismos de señalización de ADGRL4 para posibles terapias contra el cáncer.

Principales métodos:

Ensayo sensible de bioluminiscencia para detectar el acoplamiento a G proteína.
Criomicroscopía electrónica (cryo-EM) para determinar la estructura del complejo ADGRL4-Gq.

Principales resultados:

ADGRL4 exhibe un acoplamiento débil a la proteína Gq, sin acoplamiento significativo a otras G proteínas o beta-arrestina.
La estructura de criomicroscopía electrónica (cryo-EM) de 3,1 Å revela que el plegamiento de ADGRL4 es similar a otros aGPCR, pero con interacciones distintas y menos con Gq.
La estructura apoya la activación de ADGRL4 por su agonista anclado.

Conclusiones:

El acoplamiento débil de ADGRL4 a Gq es un hallazgo novedoso con implicaciones para su función en el cáncer.
La estructura determinada proporciona una base para el desarrollo de inhibidores dirigidos contra ADGRL4 en diversos tipos de tumores.

Palabras clave:

receptores acoplados a proteínas G de adhesión ADGRL4 acoplamiento a Gq cáncer estructura criogénica de EM

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