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Estudio evolutivo y base estructural de la detección de protones por Mus GPR4 y Xenopus GPR4

Xin Wen¹, Pan Shang², Haidi Chen³

¹Key Laboratory Experimental Teratology of the Ministry of Education, New Cornerstone Science Laboratory, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China; NHC Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Advanced Medical Research Institute, Shandong University, Jinan, China.

|January 3, 2025

Resumen

Este estudio revela cómo el receptor acoplado a la proteína G 4 (GPR4) detecta el pH en los animales. El análisis estructural reveló mecanismos comunes y distintos para la detección de protones, cruciales para la adaptación fisiológica.

Área de la Ciencia:

La bioquímica
Biología estructural
Biología evolutiva

Sus antecedentes:

Los animales utilizan receptores de membrana sensibles al pH como el receptor acoplado a proteínas G 4 (GPR4) para la regulación fisiológica.
La historia evolutiva y los mecanismos precisos de detección de protones de GPR4 no se comprenden completamente.

Objetivo del estudio:

Para aclarar la trayectoria evolutiva y las bases estructurales de la detección de protones por GPR4.
Investigar la correlación entre el pH óptimo de la actividad de GPR4 y los rangos de pH sanguíneo específicos de cada especie.

Principales métodos:

Determinación de las estructuras de 7-cryoelectron microscopy (cryo-EM) de Xenopus tropicalis GPR4 (xtGPR4) y Mus musculus GPR4 (mmGPR4) en varios niveles de pH.
Se analizaron los cambios estructurales y los sitios de protonación responsables de la activación de GPR4.

Principales resultados:

Se observó una correlación positiva entre el pH óptimo de GPR4 y el pH sanguíneo de diferentes especies.
La protonación de residuos específicos (H^ECL2-45.47 y H^7.36) establece una red polar y estabiliza la estructura de GPR4, un mecanismo de activación conservado.
La protonación distinta de H^ECL2-45.41 en xtGPR4 explica su pH óptimo más ácido.

Conclusiones:

Los mecanismos estructurales comunes y distintos rigen la detección de protones por GPR4 en todas las especies.
Estos hallazgos proporcionan información sobre la relación estructura-función-evolución de los receptores sensibles al pH.

Palabras clave:

GPCR y sus derivados GPR4 (en inglés)Crio-EM La evolución detección de protones

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