小柯机器人

以色列魏茨曼科学研究所Rotem Sorek、美国哈佛大学Philip J. Kranzusch等研究人员合作发现，病毒抑制TIR gcADPR信号传递来克服细菌防御。2022年9月29日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员确定了一个大型的噬菌体编码蛋白家族，被命名为Thoeris抗防御1（Tad1），它可以抑制Thoeris免疫。研究人员发现Tad1蛋白是一种“海绵”，它能结合并封存由TIR-结构域蛋白产生的免疫信号分子，从而使噬菌体感应与免疫效应器激活脱钩，然后使Thoeris失去活性。Tad1也能有效地封存来自植物TIR-结构域蛋白的分子，Tad1与植物衍生分子结合的高分辨率晶体结构显示了1''-2'糖环ADPR（gcADPR）的独特化学结构。研究人员的数据进一步表明，Thoeris TIR蛋白产生一种密切相关的分子，1''-3'gcADPR，其激活ThsA的效率比植物来源的1''-2'gcADPR高一个数量级。这些研究结果确定了一个核心免疫信号分子的化学结构，并揭示了病原体可以抑制宿主免疫的一种新的行动模式。

据介绍，TIR结构域是识别细菌、植物和动物中病原体入侵的免疫受体的一个关键组成部分。在细菌反噬系统Thoeris以及植物中，对感染的识别会刺激TIR结构域产生一种免疫信号分子，其分子结构仍然难以捉摸。这种分子结合并激活Thoeris免疫效应器，然后执行免疫功能。

附：英文原文

Title: Viruses inhibit TIR gcADPR signaling to overcome bacterial defense

Author: Leavitt, Azita, Yirmiya, Erez, Amitai, Gil, Lu, Allen, Garb, Jeremy, Herbst, Ehud, Morehouse, Benjamin R., Hobbs, Samuel J., Antine, Sadie P., Sun, Zhen-Yu J., Kranzusch, Philip J., Sorek, Rotem

Issue&Volume: 2022-09-29

Abstract: The Toll/interleukin-1 receptor (TIR) domain is a key component of immune receptors that identify pathogen invasion in bacteria, plants, and animals1–3. In the bacterial antiphage system Thoeris, as well as in plants, recognition of infection stimulates TIR domains to produce an immune signaling molecule whose molecular structure remained elusive. This molecule binds and activates the Thoeris immune effector, which then executes the immune function1. We identified a large family of phage-encoded proteins, denoted here Thoeris anti-defense 1 (Tad1), that inhibit Thoeris immunity. We found that Tad1 proteins are “sponges” that bind and sequester the immune signaling molecule produced by TIR-domain proteins, thus decoupling phage sensing from immune effector activation and rendering Thoeris inactive. Tad1 can also efficiently sequester molecules derived from a plant TIR-domain protein, and a high-resolution crystal structure of Tad1 bound to a plant-derived molecule revealed a unique chemical structure of 1''–2' glycocyclic ADPR (gcADPR). Our data furthermore suggest that Thoeris TIR proteins produce a closely related molecule, 1''–3' gcADPR, which activates ThsA an order of magnitude more efficiently than the plant-derived 1''–2' gcADPR. Our results define the chemical structure of a central immune signaling molecule, and reveal a new mode of action by which pathogens can suppress host immunity.

DOI: 10.1038/s41586-022-05375-9

Source: https://www.nature.com/articles/s41586-022-05375-9

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
官方网址：http://www.nature.com/
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