7qqk
From Proteopedia
TIR-SAVED effector bound to cA3
Structural highlights
FunctionPublication Abstract from PubMedCyclic 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 pathway(1), which originated in bacteria(2). 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 biomolecules(3). 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 bacteria(2,4,5) or during programmed nerve cell death(6). 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. Cyclic nucleotide-induced helical structure activates a TIR immune effector.,Hogrel G, Guild A, Graham S, Rickman H, Gruschow S, Bertrand Q, Spagnolo L, White MF Nature. 2022 Aug;608(7924):808-812. doi: 10.1038/s41586-022-05070-9. Epub 2022 , Aug 10. PMID:35948638[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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