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Un ARN viral secuestra la maquinaria del huésped utilizando cambios conformacionales dinámicos de una estructura
Steve L Bonilla1, Madeline E Sherlock1, Andrea MacFadden1
1Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Science (New York, N.Y.)
|November 18, 2021
Resumen
Este estudio revela cómo las estructuras de ARN del mosaico de bromo se unen dinámicamente a las proteínas del huésped. La microscopía criolectrónica visualizó estas interacciones no canónicas, ofreciendo información sobre la replicación y la traducción virales.
Área de la Ciencia:
- Biología estructural
- Virología
- Biología molecular
Sus antecedentes:
- Los virus utilizan ARN estructurados para manipular los procesos de las células huésped.
- Comprender estas estructuras de ARN es crucial para descifrar los mecanismos virales.
- Los ARN conformalmente dinámicos presentan desafíos estructurales significativos.
Objetivo del estudio:
- Determinar la estructura del ARN de transferencia de mosaico de bromo (ARNt) como estructura (TLS).
- Investigar cómo el TLS viral interactúa con los factores del huésped, específicamente con la tirosil-tRNA sintetasa (TyrRS).
- Para aclarar los cambios conformacionales dinámicos involucrados en la unión del ARN viral a la proteína huésped.
Principales métodos:
- Se utilizó la microscopía criolectrónica (cryo-EM) para visualizar las estructuras de ARN.
- Determinación de las estructuras del TLS viral en aislamiento y cuando está unido al TyrRS.
- Análisis de las reorganizaciones conformacionales del TLS en el momento de la unión.
Principales resultados:
- Visualizó el TLS viral de ~ 55 kilodaltones, un supuesto imitador de tRNA.
- Se han observado reordenamientos conformacionales significativos en el TLS al enlazar el TyrRS.
- Se identificaron interacciones no canónicas entre el ARN viral y la maquinaria del huésped.
Conclusiones:
- Los ARN virales emplean una combinación de estructuras estáticas y dinámicas para interactuar con las proteínas del huésped.
- El TLS sufre cambios conformacionales sustanciales para unirse a TyrRS, que difieren de la unión canónica al tRNA.
- Cryo-EM es una herramienta poderosa para el estudio de ARN pequeños y dinámicos estructurados en sistemas virales.
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