Journal Article

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

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

2019

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adenine / Adenosine diphosphate / Amino Acid Substitution / Apoptosis / Arabidopsis - enzymology / Arabidopsis - immunology / Arabidopsis - microbiology / Arabidopsis Proteins - metabolism / Armadillo Domain Proteins - chemistry / Binding / Biomarkers / Biomarkers - analysis / Biomarkers - metabolism / Catalysis / Catalytic Domain / Cell Death / Conserved Sequence / Cyclic ADP-ribose / Cyclic ADP-Ribose - analysis / Cyclic ADP-Ribose - metabolism / Cytokines / Cytoskeletal Proteins - chemistry / Death / Degeneration / Depletion / Disease resistance / DNA-Binding Proteins - metabolism / Domains / Enzymatic activity / Enzymes / Glutamic acid / Glutamic Acid - chemistry / Glutamic Acid - genetics / Host-Pathogen Interactions / Hypersensitive response / Immune response / Interfaces / Interleukin 1 / Leucine / Mammals / Mortality / NAD / NAD - metabolism / NAD+ Nucleosidase - chemistry / Neurodegeneration / Nicotinamide / Nicotinamide adenine dinucleotide / Nucleotides / Pathogens / Receptor mechanisms / Receptors / Receptors, Immunologic - chemistry / Recognition / Regulators / Ribose / Self-association / Signaling