7QQK

TIR-SAVED effector bound to cA3

Summary for 7QQK

• Entry DOI: 10.2210/pdb7qqk/pdb
• EMDB information: 14122
• Descriptor: TIR_SAVED fusion protein, RNA (5'-R(P*AP*AP*A)-3') (2 entities in total)
• Functional Keywords: microbacterium ketosireducens tir saved complex bound to ca3, signaling protein
• Biological source: Microbacterium ketosireducens; More
• Total number of polymer chains: 8
• Total formula weight: 191034.14

Authors

Spagnolo, L.,White, M.F.,Hogrel, G.,Guild, A. (deposition date: 2022-01-09, release date: 2022-06-15, Last modification date: 2025-07-02)

Primary citation

Hogrel, G.,Guild, A.,Graham, S.,Rickman, H.,Gruschow, S.,Bertrand, Q.,Spagnolo, L.,White, M.F.
Cyclic nucleotide-induced helical structure activates a TIR immune effector.
Nature, 608:808-812, 2022

PubMed 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 pathway, which originated in bacteria. 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. 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 or during programmed nerve cell death. 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.

PubMed: 35948638
DOI: 10.1038/s41586-022-05070-9

Experimental method

ELECTRON MICROSCOPY (3.8 Å)