Cyclic nucleotide-induced helical structure activates a TIR immune effector.
Nature
; 608(7924): 808-812, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35948638
ABSTRACT
Cyclic nucleotide signalling is a key component of antiviral defence in all domains of life. Viral detection activates a nucleotide cyclase to generate a second messenger, resulting in activation of effector proteins. This is exemplified by the metazoan cGAS-STING innate immunity pathway1, which originated in bacteria2. These defence systems require a sensor domain to bind the cyclic nucleotide and are often coupled with an effector domain that, when activated, causes cell death by destroying essential biomolecules3. One example is the Toll/interleukin-1 receptor (TIR) domain, which degrades the essential cofactor NAD+ when activated in response to infection in plants and bacteria2,4,5 or during programmed nerve cell death6. Here we show that a bacterial antiviral defence system generates a cyclic tri-adenylate that binds to a TIR-SAVED effector, acting as the 'glue' to allow assembly of an extended superhelical solenoid structure. Adjacent TIR subunits interact to organize and complete a composite active site, allowing NAD+ degradation. Activation requires extended filament formation, both in vitro and in vivo. Our study highlights an example of large-scale molecular assembly controlled by cyclic nucleotides and reveals key details of the mechanism of TIR enzyme activation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bactérias
/
Receptores de Interleucina-1
/
Receptores Toll-Like
/
Nucleotídeos Cíclicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article