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.
