Substrate-induced condensation activates plant TIR domain proteins

• 成果类型: Article
• 署名作者: 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
• 署名单位: China Agricultural University; Max Planck Society; University of Cologne; Beijing Normal University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Howard Hughes Medical Institute; Harvard Medical School; Westlake University; Tsinghua University; Max Planck Society
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6185
• DOI: 10.1038/s41586-024-07183-9
• 发表日期: 2024-03-28
• 关键词: liquid phase-separation; cell-death; resistance protein; pathogen effector; self-association; immune; arabidopsis; expression; nbs; resistosome

摘要

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. Binding of the substrates NAD+ and ATP to the plant Toll/interleukin-1 receptor (TIR) domain proteins induces phase separation and, thereby, activation of TIR enzymatic and immune signalling activity.