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Actividad de escisión de NAD+ por los dominios TIR animales y vegetales en las vías de muerte celular
Shane Horsefield1, Hayden Burdett1, Xiaoxiao Zhang2,3
1School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.
Science (New York, N.Y.)
|August 24, 2019
Resumen
Los receptores inmunes estériles alfa y TIR que contienen 1 (SARM1) y las plantas utilizan dominios Toll / interleucina-1 (TIR) para la señalización de la muerte celular. Estos dominios TIR dividen el dinucleótido de nicotinamida adenina (NAD+), un mecanismo conservado en animales y plantas.
Área de la Ciencia:
- La bioquímica
- Biología celular
- La neurociencia
Sus antecedentes:
- El alfa estéril y el motivo TIR que contiene 1 (SARM1) median la degeneración de Wallerian agotando el dinucleótido de adenina de nicotinamida (NAD+).
- Los receptores inmunes ricos en leucina (NLR) que se unen a los nucleótidos de las plantas utilizan los dominios del receptor Toll / interleucina-1 (TIR) para desencadenar la muerte celular contra los patógenos.
Objetivo del estudio:
- Investigar la actividad enzimática y la base estructural de la señalización de la muerte celular mediada por el dominio TIR.
- Determinar los mecanismos conservados de la escisión de NAD+ en las vías de muerte celular animal y vegetal.
Principales métodos:
- Ensayos bioquímicos para evaluar la actividad de escisión de NAD+.
- Técnicas de biología estructural, incluida la cristalografía de rayos X, para determinar complejos proteico-ligandos.
- Métodos biofísicos para caracterizar la autoasociación de las proteínas.
Principales resultados:
- Los dominios SARM1 y NLR TIR de las plantas exhiben actividad de escisión NAD+ dependiente de la autoasociación.
- Los dominios estériles del motivo alfa (SAM) de SARM1 forman un octámero crucial para la degeneración del axón y la actividad del dominio TIR.
- Las estructuras cristalinas revelan un sitio de unión de sustrato conservado para NAD+ en los dominios SARM1 y NLR RUN1 TIR de las plantas.
Conclusiones:
- La escisión de NAD+ por dominios TIR es una actividad enzimática conservada esencial para la señalización de la muerte celular tanto en animales como en plantas.
- La conservación estructural y funcional de los dominios TIR destaca un mecanismo molecular compartido en todos los reinos.
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