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Evolución del Dominio Tri-PDZ en PSD95 (Gen DLG-4)

Riya Nilkant¹, Lisa Y Mesrop², Samuel Lobo³

¹Department of Molecular, Cell and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106, USA.

Molecular biology and evolution

|December 17, 2025

Resumen

El gen DLG4, que codifica la proteína sináptica PSD-95, tiene orígenes antiguos en Filozoa. Sus dominios PDZ evolucionaron a partir de un único dominio ancestral, siendo los enlaces de hidrógeno cruciales para la interacción del ligando PDZ3.

Área de la Ciencia:

Biología evolutiva
Biología molecular
Genómica

Sus antecedentes:

Las proteínas sinápticas como DLG4 (que codifica PSD-95) tienen orígenes antiguos anteriores a la vida animal.
DLG4 es una proteína MAGUK con una estructura de dominio conservada que incluye dominios PDZ.

Objetivo del estudio:

Rastrear la historia evolutiva de los dominios tri-PDZ de DLG4 hasta su origen ancestral profundo.
Investigar los mecanismos de unión conservados del dominio PDZ3 y su ligando CRIPT.

Principales métodos:

Análisis filogenético de los dominios tri-PDZ de DLG4.
Modelado a Escala Evolutiva (ESM2) para la conservación de dominios.
AlphaFold2 Multimer para análisis estructural y de unión.

Principales resultados:

El linaje del dominio PDZ de DLG4 se originó a partir de un único dominio ancestral en Filozoa.
Las identidades de los dominios PDZ se conservan en el límite del reino animal.
CRIPT, un ligando PDZ3, se conserva en Filozoa, siendo los enlaces de hidrógeno clave para la unión conservada.

Conclusiones:

La arquitectura del dominio PDZ de DLG4 es antigua y altamente conservada.
Los enlaces de hidrógeno representan una innovación fundamental para las interacciones PDZ3-ligando, permitiendo interacciones proteína-proteína más amplias.

Palabras clave:

dominios PDZ evolución proteínas andamio sinápticas

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