Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity

• Published in: Science (American Association for the Advancement of Science) 2022-07, Vol.377 (6605), p.eabq3297-eabq3297
• Main Authors: Huang, Shijia, Jia, Aolin, Song, Wen, Hessler, Giuliana, Meng, Yonggang, Sun, Yue, Xu, Lina, Laessle, Henriette, Jirschitzka, Jan, Ma, Shoucai, Xiao, Yu, Yu, Dongli, Hou, Jiao, Liu, Ruiqi, Sun, Huanhuan, Liu, Xiaohui, Han, Zhifu, Chang, Junbiao, Parker, Jane E., Chai, Jijie
• Format: Article
• Language: English
• Subjects: Adenine; Adenosine diphosphate; Adenosine monophosphate; AMP; Animal diseases; Arabidopsis; Binding sites; Cell death; Chemical synthesis; Coils; Crystal structure; Cytokines; Dimers; Disease resistance; Effectors; Feedback (Response); Flowering; Flowering plants; Grooves; Immune response; Immunity; Insect cells; Insects; Interleukin 1; Leucine; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Mustard; NAD; Nucleotides; Oligomerization; Pathogens; Plant diseases; Plant immunity; Plants (botany); Proteins; Recognition; Second messengers; Senescence; Signal transduction
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abq3297

Plant nucleotide-binding leucine-rich repeat-containing (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded nicotinamide adenine dinucleotide hydrolase (NADase) activity for immune signaling. TIR-NLR signaling requires the helper NLRs N requirement gene 1 (NRG1), Activated Disease Resistance 1 (ADR1), and Enhanced Disease Susceptibility 1 (EDS1), which forms a heterodimer with each of its paralogs Phytoalexin Deficient 4 (PAD4) and Senescence-Associated Gene 101 (SAG101). Here, we show that TIR-containing proteins catalyze the production of 2′-(5′′-phosphoribosyl)-5′-adenosine monophosphate (pRib-AMP) and diphosphate (pRib-ADP) in vitro and in planta. Biochemical and structural data demonstrate that EDS1-PAD4 is a receptor complex for pRib-AMP and pRib-ADP, which allosterically promote EDS1-PAD4 interaction with ADR1-L1 but not NRG1A. Our study identifies TIR-catalyzed pRib-AMP and pRib-ADP as a missing link in TIR signaling through EDS1-PAD4 and as likely second messengers for plant immunity. Key receptors in flowering plants respond to pathogen effector molecules and trigger the plant’s immune response when needed. Huang et al . and Jia et al . now tell the story of a branching signaling pathway through which receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain enzymatically produce small, nucleotide-based second messengers and initiate immune responses in the small mustard plant Arabidopsis . The pathways diverge to activate different immune responses, with one pathway controlling the cell death response and the other managing transcriptional change. —PJH Second messengers link diverging pathways in plant pathogen detection to immune response.