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

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263 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

Bibliographical note

Funding Information:
This work was supported by the National Science Foundation (grant IOS-1758400 to J.L.D. and M.T.N.) and National Institutes of Health (grants GM107444 to J.L.D., RF1AG013730 to J.M., and R01NS087632 to J.M. and A.D.). J.L.D. is a Howard Hughes Medical Institute (HHMI) Investigator. M.T.N. was supported by startup funds from Colorado State University. R.G.A. was supported by an NIH Ruth L. Kirschstein NRSA fellowship (F32GM108226). K.E. was an HHMI Medical Research Fellow. F.M. is supported by a grant from the Gordon and Betty Moore Foundation (GBMF4725) to the Two Blades Foundation.

Publisher Copyright:
© The Authors, some rights reserved.

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