Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, Center for Plant Biology, School of Life Sciences, Tsinghua University, 100084 Beijing, China.
Institute of Biochemistry, University of Cologne, 50674 Cologne, Germany.
Science. 2022 Jul 29;377(6605):eabq8180. doi: 10.1126/science.abq8180.
Plant pathogen-activated immune signaling by nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain converges on Enhanced Disease Susceptibility 1 (EDS1) and its direct partners, Phytoalexin Deficient 4 (PAD4) or Senescence-Associated Gene 101 (SAG101). TIR-encoded nicotinamide adenine dinucleotide hydrolase (NADase) produces signaling molecules to promote exclusive EDS1-PAD4 and EDS1-SAG101 interactions with helper NLR subclasses. In this work, we show that TIR-containing proteins catalyze adenosine diphosphate (ADP)-ribosylation of adenosine triphosphate (ATP) and ADP ribose (ADPR) through ADPR polymerase-like and NADase activity, forming ADP-ribosylated ATP (ADPr-ATP) and ADPr-ADPR (di-ADPR), respectively. Specific binding of ADPr-ATP or di-ADPR allosterically promotes EDS1-SAG101 interaction with helper NLR N requirement gene 1A (NRG1A) in vitro and in planta. Our data reveal an enzymatic activity of TIRs that enables specific activation of the EDS1-SAG101-NRG1 immunity branch.
植物病原体激活的免疫信号由核苷酸结合富含亮氨酸重复（NLR）受体与 N 端 Toll/白细胞介素-1 受体（TIR）结构域融合，汇聚到增强疾病易感性 1（EDS1）及其直接伴侣，植物抗毒素缺乏 4（PAD4）或衰老相关基因 101（SAG101）。TIR 编码的烟酰胺腺嘌呤二核苷酸水解酶（NADase）产生信号分子，以促进 EDS1-PAD4 和 EDS1-SAG101 与辅助 NLR 亚类的特有相互作用。在这项工作中，我们表明 TIR 包含的蛋白质通过 ADPR 聚合酶样和 NADase 活性催化三磷酸腺苷（ATP）和二磷酸腺苷核糖（ADPR）的二磷酸腺苷（ADP）-核糖基化，分别形成 ADP-核糖基化的 ATP（ADPr-ATP）和 ADPr-ADPR（二 ADPR）。ADPr-ATP 或二 ADPR 的特异性结合在体外和体内均别构促进 EDS1-SAG101 与辅助 NLR N 需求基因 1A（NRG1A）的相互作用。我们的数据揭示了 TIRs 的一种酶活性，使 EDS1-SAG101-NRG1 免疫分支能够特异性激活。
