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):eabq3297. doi: 10.1126/science.abq3297.
Plant nucleotide-binding leucine-rich repeat-containing (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded nicotinamide adenine dinucleotide hydrolase (NADase) activity for immune signaling. TIR-NLR signaling requires the helper NLRs N requirement gene 1 (NRG1), Activated Disease Resistance 1 (ADR1), and Enhanced Disease Susceptibility 1 (EDS1), which forms a heterodimer with each of its paralogs Phytoalexin Deficient 4 (PAD4) and Senescence-Associated Gene 101 (SAG101). Here, we show that TIR-containing proteins catalyze the production of 2'-(5''-phosphoribosyl)-5'-adenosine monophosphate (pRib-AMP) and diphosphate (pRib-ADP) in vitro and in planta. Biochemical and structural data demonstrate that EDS1-PAD4 is a receptor complex for pRib-AMP and pRib-ADP, which allosterically promote EDS1-PAD4 interaction with ADR1-L1 but not NRG1A. Our study identifies TIR-catalyzed pRib-AMP and pRib-ADP as a missing link in TIR signaling through EDS1-PAD4 and as likely second messengers for plant immunity.
植物核苷酸结合富含亮氨酸重复序列的受体（NLR）带有一个 N 端 Toll/白细胞介素-1 受体（TIR）结构域，可识别病原体效应物，从而使 TIR 编码的烟酰胺腺嘌呤二核苷酸水解酶（NADase）活性得以发挥，用于免疫信号传导。TIR-NLR 信号需要辅助 NLR N 需求基因 1（NRG1）、激活疾病抗性 1（ADR1）和增强疾病易感性 1（EDS1），它们与各自的同源物 Phytoalexin Deficient 4（PAD4）和 Senescence-Associated Gene 101（SAG101）形成异源二聚体。在这里，我们表明 TIR 包含的蛋白质可在体外和植物体内催化 2'-(5''-磷酸核糖基）-5'-腺嘌呤单磷酸（pRib-AMP）和二磷酸（pRib-ADP）的生成。生化和结构数据表明，EDS1-PAD4 是 pRib-AMP 和 pRib-ADP 的受体复合物，它们别构促进 EDS1-PAD4 与 ADR1-L1 而非 NRG1A 的相互作用。我们的研究鉴定出 TIR 催化的 pRib-AMP 和 pRib-ADP 作为通过 EDS1-PAD4 的 TIR 信号的缺失环节，以及作为植物免疫的可能第二信使。
