9B7D

Structure of ThsB-Tad3 complex

9B7D の概要

• エントリーDOI: 10.2210/pdb9b7d/pdb
• 分子名称: Putative cyclic ADP-D-ribose synthase ThsB1, Tad3 (3 entities in total)
• 機能のキーワード: immune evasion, thoeris, viral protein
• 由来する生物種: Bacillus cereus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 89994.62

構造登録者

Hobbs, S.J.,Tan, J.M.J.,Yirmiya, E.,Sorek, R.,Kranzusch, P.J. (登録日: 2024-03-27, 公開日: 2025-01-22, 最終更新日: 2025-04-02)

主引用文献

Yirmiya, E.,Hobbs, S.J.,Leavitt, A.,Osterman, I.,Avraham, C.,Hochhauser, D.,Madhala, B.,Skovorodka, M.,Tan, J.M.J.,Toyoda, H.C.,Chebotar, I.,Itkin, M.,Malitsky, S.,Amitai, G.,Kranzusch, P.J.,Sorek, R.
Structure-guided discovery of viral proteins that inhibit host immunity.
Cell, 188:1681-, 2025

PubMed Abstract: Viruses encode proteins that inhibit host defenses, but sifting through the millions of available viral sequences for immune-modulatory proteins has been so far impractical. Here, we develop a process to systematically screen virus-encoded proteins for inhibitors that physically bind host immune proteins. Focusing on Thoeris and CBASS, bacterial defense systems that are the ancestors of eukaryotic Toll/interleukin-1 receptor (TIR) and cyclic GMP-AMP synthase (cGAS) immunity, we discover seven families of Thoeris and CBASS inhibitors, encompassing thousands of genes widespread in phages. Verified inhibitors exhibit extensive physical interactions with the respective immune protein counterpart, with all inhibitors blocking the active site of the immune protein. Remarkably, a phage-encoded inhibitor of bacterial TIR proteins can bind and inhibit distantly related human and plant immune TIRs, and a phage-derived inhibitor of bacterial cGAS-like enzymes can inhibit the human cGAS. Our results demonstrate that phages are a reservoir for immune-modulatory proteins capable of inhibiting bacterial, animal, and plant immunity.

PubMed: 39855193
DOI: 10.1016/j.cell.2024.12.035

実験手法

X-RAY DIFFRACTION (1.8 Å)