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La señalización antiviral tipo III CRISPR a través de la conjugación de ATP y SAM
Haotian Chi1, Ville Hoikkala1,2, Sabine Grüschow1
1Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK.
Nature
|October 18, 2023
Resumen
Los sistemas CRISPR tipo III-B en Bacteroides fragilis usan S-adenosil metionina-AMP (SAM-AMP) para la defensa antiviral, no los oligoadenilatos cíclicos. Este nuevo segundo mensajero se dirige a las proteínas de la membrana, ofreciendo nuevos conocimientos sobre la inmunidad procariótica.
Área de la Ciencia:
- Biología molecular
- Microbiología
- Inmunología
Sus antecedentes:
- Los sistemas CRISPR procariotas proporcionan inmunidad adaptativa contra los elementos genéticos móviles.
- Los sistemas CRISPR de tipo III utilizan ARN CRISPR y Cas10 para detectar y eliminar ácidos nucleicos extraños.
- Algunos sistemas de tipo III involucran proteínas no caracterizadas como CorA y fosfodiesterasas para la defensa.
Objetivo del estudio:
- Para investigar el mecanismo de defensa antiviral del sistema CRISPR tipo III-B (Cmr) asociado con CorA de Bacteroides fragilis.
- Elucidar las moléculas de señalización y los efectores involucrados en la respuesta inmune del sistema Cmr de B. fragilis.
- Para caracterizar el nuevo segundo mensajero generado por este sistema CRISPR.
Principales métodos:
- Expresión del sistema CRISPR de B. fragilis en Escherichia coli.
- Análisis de las moléculas de señalización producidas por la activación del sistema CRISPR.
- Caracterización bioquímica de la interacción entre la molécula generada y el efector CorA.
Principales resultados:
- El sistema Cmr de B. fragilis confiere inmunidad contra los elementos genéticos móviles de E. coli.
- En lugar de oligoadenilatos cíclicos, el sistema genera S-adenosil metionina-AMP (SAM-AMP) mediante la conjugación de ATP con S-adenosil metionina (SAM).
- SAM-AMP se une al efector CorA, lo que puede alterar la integridad de la membrana y conducir a la latencia o muerte celular.
Conclusiones:
- SAM-AMP es una nueva clase de segundo mensajero involucrado en la señalización antiviral procariótica.
- El sistema Cmr de B. fragilis representa un mecanismo distinto de inmunidad CRISPR de tipo III.
- La degradación de SAM-AMP por enzimas específicas proporciona un potencial "interruptor" para la respuesta inmune.
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