小柯机器人

英国圣安德鲁斯大学Malcolm F. White、格拉斯哥大学Laura Spagnolo等研究人员合作发现，环化核苷酸诱导的螺旋结构激活一种TIR免疫效应子。相关论文于2022年8月10日在线发表在《自然》杂志上。

Author: Hogrel, Galle, Guild, Abbie, Graham, Shirley, Rickman, Hannah, Grschow, Sabine, Bertrand, Quentin, Spagnolo, Laura, White, Malcolm F.

Issue&Volume: 2022-08-10

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.

DOI: 10.1038/s41586-022-05070-9

Source: https://www.nature.com/articles/s41586-022-05070-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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