TIR domains of plant immune receptors are NAD+-cleaving enzymes that promote cell death

Li Wan, Kow Essuman, Ryan G. Anderson, Yo Sasaki, Freddy Monteiro, Eui Hwan Chung, Erin Osborne Nishimura, Aaron DiAntonio, Jeffrey Milbrandt, Jeffery L. Dangl, Marc T. Nishimura

Research output: Contribution to journalArticlepeer-review

201 Citations (Scopus)


Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors activate cell death and confer disease resistance by unknown mechanisms. We demonstrate that plant Toll/interleukin-1 receptor (TIR) domains of NLRs are enzymes capable of degrading nicotinamide adenine dinucleotide in its oxidized form (NAD+). Both cell death induction and NAD+ cleavage activity of plant TIR domains require known self-association interfaces and a putative catalytic glutamic acid that is conserved in both bacterial TIR NAD+-cleaving enzymes (NADases) and the mammalian SARM1 (sterile alpha and TIR motif containing 1) NADase. We identify a variant of cyclic adenosine diphosphate ribose as a biomarker of TIR enzymatic activity. TIR enzymatic activity is induced by pathogen recognition and functions upstream of the genes enhanced disease susceptibility 1 (EDS1) and N requirement gene 1 (NRG1), which encode regulators required for TIR immune function. Thus, plant TIR-NLR receptors require NADase function to transduce recognition of pathogens into a cell death response.

Original languageEnglish
Pages (from-to)799-803
Number of pages5
Issue number6455
Publication statusPublished - 2019 Aug 23
Externally publishedYes

ASJC Scopus subject areas

  • General


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