Department of Biology and Howard Hughes Medical Institute, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Science. 2019 Aug 23;365(6455):799-803. doi: 10.1126/science.aax1771.
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 () and (), 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.
植物核苷酸结合富含亮氨酸重复（NLR）免疫受体通过未知机制激活细胞死亡并赋予抗病性。我们证明植物 Toll/白细胞介素-1 受体（TIR）结构域的 NLR 是能够降解氧化形式烟酰胺腺嘌呤二核苷酸（NAD）的酶。植物 TIR 结构域的细胞死亡诱导和 NAD 切割活性都需要已知的自组装界面和一个假定的催化谷氨酸，该谷氨酸在细菌 TIR NAD 切割酶（NADases）和哺乳动物 SARM1（无菌α和 TIR 基序包含 1）NADase 中都保守。我们鉴定出一种环腺苷二磷酸核糖的变体作为 TIR 酶活性的生物标志物。TIR 酶活性被病原体识别诱导，并在上游基因 () 和 () 发挥作用，这两个基因编码 TIR 免疫功能所需的调节剂。因此，植物 TIR-NLR 受体需要 NADase 功能将病原体的识别转化为细胞死亡反应。
