TIR-catalyzed ADP-ribosylation reactions produce signaling molecules for plant immunity

Science. 2022 Jul 29;377(6605):eabq8180. doi: 10.1126/science.abq8180. Epub 2022 Jul 29.


Plant pathogen-activated immune signaling by nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain converges on Enhanced Disease Susceptibility 1 (EDS1) and its direct partners, Phytoalexin Deficient 4 (PAD4) or Senescence-Associated Gene 101 (SAG101). TIR-encoded nicotinamide adenine dinucleotide hydrolase (NADase) produces signaling molecules to promote exclusive EDS1-PAD4 and EDS1-SAG101 interactions with helper NLR subclasses. In this work, we show that TIR-containing proteins catalyze adenosine diphosphate (ADP)-ribosylation of adenosine triphosphate (ATP) and ADP ribose (ADPR) through ADPR polymerase-like and NADase activity, forming ADP-ribosylated ATP (ADPr-ATP) and ADPr-ADPR (di-ADPR), respectively. Specific binding of ADPr-ATP or di-ADPR allosterically promotes EDS1-SAG101 interaction with helper NLR N requirement gene 1A (NRG1A) in vitro and in planta. Our data reveal an enzymatic activity of TIRs that enables specific activation of the EDS1-SAG101-NRG1 immunity branch.

MeSH terms

  • ADP-Ribosylation*
  • Adenosine Diphosphate* / metabolism
  • Adenosine Triphosphate / metabolism
  • Arabidopsis Proteins* / metabolism
  • Arabidopsis* / enzymology
  • Arabidopsis* / immunology
  • Carboxylic Ester Hydrolases* / chemistry
  • Carboxylic Ester Hydrolases* / genetics
  • Carboxylic Ester Hydrolases* / metabolism
  • DNA-Binding Proteins* / metabolism
  • Intracellular Signaling Peptides and Proteins* / metabolism
  • NAD+ Nucleosidase / metabolism
  • Plant Immunity*


  • AT5G66900 protein, Arabidopsis
  • Arabidopsis Proteins
  • DNA-Binding Proteins
  • EDS1 protein, Arabidopsis
  • Intracellular Signaling Peptides and Proteins
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Carboxylic Ester Hydrolases
  • SAG101 protein, Arabidopsis
  • NAD+ Nucleosidase