7UAV

Structure of Clostridium botulinum prophage Tad1 in apo state

7UAV の概要

• エントリーDOI: 10.2210/pdb7uav/pdb
• 分子名称: ABC transporter ATPase (2 entities in total)
• 機能のキーワード: anti-thoeris, immune evasion, signal sequestration, viral protein
• 由来する生物種: Clostridium botulinum
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 72593.30

構造登録者

Lu, A.,Leavitt, A.,Yirmiya, E.,Amitai, G.,Garb, J.,Morehouse, B.R.,Hobbs, S.J.,Sorek, R.,Kranzusch, P.J. (登録日: 2022-03-14, 公開日: 2022-10-05, 最終更新日: 2024-10-16)

主引用文献

Leavitt, A.,Yirmiya, E.,Amitai, G.,Lu, A.,Garb, J.,Herbst, E.,Morehouse, B.R.,Hobbs, S.J.,Antine, S.P.,Sun, Z.J.,Kranzusch, P.J.,Sorek, R.
Viruses inhibit TIR gcADPR signalling to overcome bacterial defence.
Nature, 611:326-331, 2022

PubMed Abstract: The Toll/interleukin-1 receptor (TIR) domain is a key component of immune receptors that identify pathogen invasion in bacteria, plants and animals. 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 function. 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.

PubMed: 36174646
DOI: 10.1038/s41586-022-05375-9

実験手法

X-RAY DIFFRACTION (2.2 Å)