西湖大学柴继杰和德国马克斯普朗克植物育种研究所Paul Schulze-Lefert共同合作，近期取得重要工作进展。他们研究提出，底物诱导的缩合能够激活植物TIR结构域蛋白。相关研究成果2024年3月13日在线发表于《自然》杂志上。

据了解，具有N-末端Toll/白细胞介素-1受体（TIR）结构域的植物核苷酸结合富含亮氨酸重复序列（NLR）免疫受体通常通过其C-末端配体传感结构域介导对菌株特异性病原体效应物的识别。效应物结合使TIR编码的酶活性成为TIR–NLR（TNL）介导的免疫所必需的。许多截短的TNL蛋白缺乏效应物传感结构域，但保留相似的酶活性和免疫活性。这些TIR结构域蛋白激活的机制尚不清楚。

研究人员表明，TIR底物NAD⁺和ATP的结合在体外诱导TIR结构域蛋白的相分离。通过其天然启动子表达的TIR结构域蛋白发生类似的缩合反应，以响应植物中的病原体接种。TIR缩合物的形成是由保守的自缔合界面和预测的TIR的内在无序环区介导的。破坏TIR缩合物的突变损害TIR结构域蛋白的细胞死亡活性。

总之，这一数据揭示了相分离作为TIR结构域蛋白激活的机制之一，并为底物诱导的TIR信号的自主激活提供了见解，以赋予植物免疫力。

附：英文原文

Title: Substrate-induced condensation activates plant TIR domain proteins

Author: Song, Wen, Liu, Li, Yu, Dongli, Bernardy, Hanna, Jirschitzka, Jan, Huang, Shijia, Jia, Aolin, Jemielniak, Wictoria, Acker, Julia, Laessle, Henriette, Wang, Junli, Shen, Qiaochu, Chen, Weijie, Li, Pilong, Parker, Jane E., Han, Zhifu, Schulze-Lefert, Paul, Chai, Jijie

Issue&Volume: 2024-03-13

Abstract: Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain mediate recognition of strain-specific pathogen effectors, typically via their C-terminal ligand-sensing domains1. Effector binding enables TIR-encoded enzymatic activities that are required for TIR–NLR (TNL)-mediated immunity2,3. Many truncated TNL proteins lack effector-sensing domains but retain similar enzymatic and immune activities4,5. The mechanism underlying the activation of these TIR domain proteins remain unclear. Here we show that binding of the TIR substrates NAD+ and ATP induces phase separation of TIR domain proteins in vitro. A similar condensation occurs with a TIR domain protein expressed via its native promoter in response to pathogen inoculation in planta. The formation of TIR condensates is mediated by conserved self-association interfaces and a predicted intrinsically disordered loop region of TIRs. Mutations that disrupt TIR condensates impair the cell death activity of TIR domain proteins. Our data reveal phase separation as a mechanism for the activation of TIR domain proteins and provide insight into substrate-induced autonomous activation of TIR signalling to confer plant immunity.

DOI: 10.1038/s41586-024-07183-9

Source: https://www.nature.com/articles/s41586-024-07183-9