Nature :病毒抑制 TIR gcADPR 信号传导以克服细菌防御

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Nature :病毒抑制 TIR gcADPR 信号传导以克服细菌防御

Toll/白细胞介素 1 受体 (TIR) 域是免疫受体的关键组成部分，可识别细菌、植物和动物中的病原体入侵。病毒抑制 TIR gcADPR 信号以克服细菌防御、抗防御。本文是病毒学、免医学等关联基础医学研究论文。

领研网

2022/11/21

论文
论文标题：Viruses inhibit TIR gcADPR signalling to overcome bacterial defence
作者：Azita Leavitt, Erez Yirmiya, Gil Amitai, Allen Lu, Jeremy Garb, Ehud Herbst, Benjamin R. Morehouse, Samuel J. Hobbs, Sadie P. Antine, Zhen-Yu J. Sun, Philip J. Kranzusch & Rotem Sorek

期刊：Nature
发表时间：2022/09/29
数字识别码：10.1038/s41586-022-05375-9
摘要：The Toll/interleukin-1 receptor (TIR) domain is a key component of immune receptors that identify pathogen invasion in bacteria, plants and animals1,2,3. In the bacterial antiphage system Thoeris, as well as in plants, recognition of infection stimulates TIR domains to produce an immune signalling molecule whose molecular structure remains 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 as Thoeris anti-defence 1 (Tad1), that inhibit Thoeris immunity. We found that Tad1 proteins are ‘sponges’ that bind and sequester the immune signalling 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 showed 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 signalling molecule and show a new mode of action by which pathogens can suppress host immunity.

所属学科：
免疫学

（导读 阿金）Toll/IL-1受体（TIR）结构域是识别细菌、植物和动物体内病原体入侵的免疫受体关键成分。本研究识别出一个大型噬菌体编码蛋白质家族：Thoeris抗防御1（Tad1），会抑制Thoeris免疫，Tad1蛋白结合并且隔离由TIR结构域蛋白质生成的免疫信号传导分子，使噬菌体感知与免疫效应子激活解耦，让Thoeris失活。Tad1还有效隔离植物TIR结构域蛋白的衍生分子。该结果确认了核心免疫信号传导分子的化学结构。

文章标签
Toll/IL-1受体（TIR）结构域
免疫受体
噬菌体编码蛋白质家族
Thoeris抗防御1
免疫信号传导分子

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

https://www.linkresearcher.com/t ... 8-948f-215fe06bf95d



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