A Coevolved EDS1-SAG101-NRG1 Module Mediates Cell Death Signaling by TIR-Domain Immune Receptors

Plant Cell. 2019 Oct;31(10):2430-2455. doi: 10.1105/tpc.19.00118. Epub 2019 Jul 16.


Plant nucleotide binding/leucine-rich repeat (NLR) immune receptors are activated by pathogen effectors to trigger host defenses and cell death. Toll-interleukin 1 receptor domain NLRs (TNLs) converge on the ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1) family of lipase-like proteins for all resistance outputs. In Arabidopsis (Arabidopsis thaliana) TNL-mediated immunity, AtEDS1 heterodimers with PHYTOALEXIN DEFICIENT4 (AtPAD4) transcriptionally induced basal defenses. AtEDS1 uses the same surface to interact with PAD4-related SENESCENCE-ASSOCIATED GENE101 (AtSAG101), but the role of AtEDS1-AtSAG101 heterodimers remains unclear. We show that AtEDS1-AtSAG101 functions together with N REQUIRED GENE1 (AtNRG1) coiled-coil domain helper NLRs as a coevolved TNL cell death-signaling module. AtEDS1-AtSAG101-AtNRG1 cell death activity is transferable to the Solanaceous species Nicotiana benthamiana and cannot be substituted by AtEDS1-AtPAD4 with AtNRG1 or AtEDS1-AtSAG101 with endogenous NbNRG1. Analysis of EDS1-family evolutionary rate variation and heterodimer structure-guided phenotyping of AtEDS1 variants and AtPAD4-AtSAG101 chimeras identify closely aligned ɑ-helical coil surfaces in the AtEDS1-AtSAG101 partner C-terminal domains that are necessary for reconstituted TNL cell death signaling. Our data suggest that TNL-triggered cell death and pathogen growth restriction are determined by distinctive features of EDS1-SAG101 and EDS1-PAD4 complexes and that these signaling machineries coevolved with other components within plant species or clades to regulate downstream pathways in TNL immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / genetics*
  • Arabidopsis / immunology
  • Arabidopsis / microbiology
  • Arabidopsis Proteins / chemistry
  • Arabidopsis Proteins / genetics*
  • Arabidopsis Proteins / immunology*
  • Arabidopsis Proteins / metabolism*
  • Carboxylic Ester Hydrolases / chemistry
  • Carboxylic Ester Hydrolases / genetics
  • Carboxylic Ester Hydrolases / metabolism*
  • Cell Death / genetics
  • Cell Death / immunology
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Evolution, Molecular
  • F-Box Proteins / immunology*
  • Immunity, Innate
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mutation
  • NLR Proteins / metabolism
  • Phylogeny
  • Plant Diseases / immunology
  • Plant Immunity / physiology*
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Plants, Genetically Modified / genetics
  • Plants, Genetically Modified / metabolism
  • Protein Domains / genetics
  • Receptors, Cell Surface / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Solanum lycopersicum / genetics
  • Solanum lycopersicum / metabolism
  • Tobacco / genetics
  • Tobacco / metabolism


  • AT5G66900 protein, Arabidopsis
  • Arabidopsis Proteins
  • DNA-Binding Proteins
  • EDS1 protein, Arabidopsis
  • F-Box Proteins
  • Intracellular Signaling Peptides and Proteins
  • NLR Proteins
  • Plant Proteins
  • RPP5 protein, Arabidopsis
  • RRS1 protein, Arabidopsis
  • Receptors, Cell Surface
  • TIR1 protein, Arabidopsis
  • rps4 protein, plant
  • Carboxylic Ester Hydrolases
  • PAD4 protein, Arabidopsis
  • SAG101 protein, Arabidopsis