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

Science. 2022 Jul 29;377(6605):eabq3297. doi: 10.1126/science.abq3297. Epub 2022 Jul 29.


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.

MeSH terms

  • Adenosine Diphosphate* / metabolism
  • Adenosine Monophosphate* / metabolism
  • Arabidopsis Proteins* / chemistry
  • Arabidopsis Proteins* / genetics
  • Arabidopsis Proteins* / metabolism
  • Arabidopsis* / enzymology
  • Arabidopsis* / immunology
  • Carboxylic Ester Hydrolases* / chemistry
  • Carboxylic Ester Hydrolases* / genetics
  • Carboxylic Ester Hydrolases* / metabolism
  • Catalysis
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Plant Immunity* / genetics


  • Arabidopsis Proteins
  • DNA-Binding Proteins
  • EDS1 protein, Arabidopsis
  • Adenosine Monophosphate
  • Adenosine Diphosphate
  • Carboxylic Ester Hydrolases
  • PAD4 protein, Arabidopsis
  • SAG101 protein, Arabidopsis