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-Structure paper
タイトル | Cyclic nucleotide-induced helical structure activates a TIR immune effector. |
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ジャーナル・号・ページ | Nature, Vol. 608, Issue 7924, Page 808-812, Year 2022 |
掲載日 | 2022年8月10日 |
著者 | Gaëlle Hogrel / Abbie Guild / Shirley Graham / Hannah Rickman / Sabine Grüschow / Quentin Bertrand / Laura Spagnolo / Malcolm F White / |
PubMed 要旨 | 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 ...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. |
リンク | Nature / PubMed:35948638 |
手法 | EM (単粒子) |
解像度 | 3.8 Å |
構造データ | EMDB-14122, PDB-7qqk: |
由来 |
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キーワード | SIGNALING PROTEIN / Microbacterium ketosireducens TIR SAVED complex bound to cA3 |