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Descubrimiento de la Acilación de Lisina Mediada por Itaconato

Dongyang Liu¹, Weidi Xiao¹, Haoting Li²

¹Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Journal of the American Chemical Society

|June 5, 2023

Resumen

Los investigadores descubrieron una nueva modificación post-traduccional llamada itaconilación de lisina, un nuevo mecanismo para el itaconato

Área de la Ciencia:

La bioquímica
Inmunología
Metabolomía

Sus antecedentes:

El itaconato es un metabolito clave en las interacciones huésped-patógeno, conocido por sus funciones antimicrobianas e inmunorreguladoras.
El principal mecanismo conocido del itaconato implica la modificación covalente de los residuos de cisteína (itaconación).
Otros mecanismos de regulación del itaconato permanecieron en gran parte sin explorar.

Objetivo del estudio:

Investigar nuevas modificaciones post-traducionales mediadas por itaconato.
Identificar y caracterizar nuevos mecanismos del papel del itaconato en la inmunorregulación.

Principales métodos:

Utilizó el enriquecimiento de anticuerpos promiscuos y la estrategia de búsqueda abierta en el análisis de datos.
Se empleó la proteómica cuantitativa para identificar los sitios de itaconilación.
Se han confirmado los sitios identificados utilizando estándares de péptidos sintéticos.

Principales resultados:

Descubrieron y confirmaron una nueva modificación post-traduccional: la itaconilación de lisina.
Se observó una regulación significativa de la itaconilación y el itaconil-CoA tras la estimulación de los lipopolisacáridos en los macrófagos.
Sitios de itaconilación identificados en proteínas funcionales, incluidas las enzimas glicolíticas y las histonas.

Conclusiones:

La itaconilación de la lisina representa un mecanismo regulador recientemente identificado para el itaconato.
Este descubrimiento amplía nuestra comprensión de cómo el itaconato influye en la inmunorregulación.
Abre nuevas vías para la investigación del papel del itaconato en los procesos celulares y las enfermedades.

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