小柯机器人

以色列魏茨曼科学研究所Rotem Sorek和Gil Amitai研究团队合作发现细菌Toll/白细胞介素-1 受体 (TIR)结构域通过触发免疫信号分子激活抗病毒活性。这一研究成果于2021年12月1日发表在国际顶尖学术期刊《自然》上。

他们表明噬菌体感染会触发 Thoeris TIR 结构域蛋白产生环状 ADP 核糖的异构体。该分子信号激活第二种蛋白质 ThsA，然后耗尽细胞中必需分子烟酰胺腺嘌呤二核苷酸 (NAD) 的含量，并导致感染失败和细胞死亡。他们还表明，类似于真核先天免疫系统，细菌 TIR 结构域蛋白决定了对入侵病原体的免疫特异性。他们的结果描述了细菌中的抗病毒信号通路，并表明细胞内信号分子的产生是 TIR 结构域的一种古老的免疫学功能，在植物和细菌免疫中都是保守的。

据了解，TIR结构域是动植物免疫系统的典型组成部分。在植物中，免疫受体对细胞内病原体的感知触发它们的 TIR 结构域产生一种分子，该分子是环状 ADP-核糖的变体。假设该分子通过尚未解决的途径介导植物细胞死亡。TIR 结构域也已被证明与一种称为Thoeris的细菌抗噬菌体防御系统有关，但Thoeris防御的机制仍然未知。

附：英文原文

Title: Antiviral activity of bacterial TIR domains via immune signalling molecules

Author: Ofir, Gal, Herbst, Ehud, Baroz, Maya, Cohen, Daniel, Millman, Adi, Doron, Shany, Tal, Nitzan, Malheiro, Daniel B. A., Malitsky, Sergey, Amitai, Gil, Sorek, Rotem

Issue&Volume: 2021-12-01

Abstract: The Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems1,2. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule that is a variant of cyclic ADP-ribose3,4. This molecule is hypothesized to mediate plant cell death through a pathway that has yet to be resolved5. TIR domains have also been shown to be involved in a bacterial anti-phage defence system called Thoeris6, but the mechanism of Thoeris defence remained unknown. Here we show that phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose. This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death. We also show that, similar to eukaryotic innate immune systems, bacterial TIR-domain proteins determine the immunological specificity to the invading pathogen. Our results describe an antiviral signalling pathway in bacteria, and suggest that the generation of intracellular signalling molecules is an ancient immunological function of TIR domains that is conserved in both plant and bacterial immunity.

DOI: 10.1038/s41586-021-04098-7

Source: https://www.nature.com/articles/s41586-021-04098-7

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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