7QQK

TIR-SAVED effector bound to cA3

7QQK の概要

• エントリーDOI: 10.2210/pdb7qqk/pdb
• EMDBエントリー: 14122
• 分子名称: TIR_SAVED fusion protein, RNA (5'-R(P*AP*AP*A)-3') (2 entities in total)
• 機能のキーワード: microbacterium ketosireducens tir saved complex bound to ca3, signaling protein
• 由来する生物種: Microbacterium ketosireducens; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 191034.14

構造登録者

Spagnolo, L.,White, M.F.,Hogrel, G.,Guild, A. (登録日: 2022-01-09, 公開日: 2022-06-15, 最終更新日: 2025-07-02)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.8 Å)