2\',3\'-cAMP是已建立的第二信使3\'的位置异构体,5\'-cAMP,但对这种非经典环核苷酸一磷酸(cNMP)的生物学知之甚少。核苷酸结合的富含亮氨酸重复序列(NLR)免疫受体的Toll/白介素-1受体(TIR)结构域具有NAD酶功能,但不足以激活植物免疫反应。这里,我们表明植物TIR蛋白,除了是NADases,作为2\',3'-cAMP/cGMP合成酶通过水解RNA/DNA。结构数据显示TIR结构域采用具有互斥的NAD酶和合成酶活性的不同寡聚物。特异性破坏合成酶活性的突变消除了本氏烟草(Nb)中TIR介导的细胞死亡,支持这些cNMP在TIR信号传导中的重要作用。此外,拟南芥TIR-NLR信号的负调节因子,NUDT7,显示2\',3\'-cAMP/cGMP但不是3\',5'-cAMP/cGMP磷酸二酯酶活性和抑制Nb中TIR的细胞死亡活性。我们的研究确定了一个2\'的家庭,3'-cAMP/cGMP合成酶,并确立了它们在植物免疫反应中的关键作用。
2\',3\'-cAMP is a positional isomer of the well-established second messenger 3\',5\'-cAMP, but little is known about the biology of this noncanonical cyclic nucleotide monophosphate (cNMP). Toll/interleukin-1 receptor (TIR) domains of nucleotide-binding leucine-rich repeat (NLR) immune receptors have the NADase function necessary but insufficient to activate plant immune responses. Here, we show that plant TIR proteins, besides being NADases, act as 2\',3\'-cAMP/cGMP synthetases by hydrolyzing RNA/DNA. Structural data show that a TIR domain adopts distinct oligomers with mutually exclusive NADase and synthetase activity. Mutations specifically disrupting the synthetase activity abrogate TIR-mediated cell death in Nicotiana benthamiana (Nb), supporting an important role for these cNMPs in TIR signaling. Furthermore, the Arabidopsis negative regulator of TIR-NLR signaling, NUDT7, displays 2\',3\'-cAMP/cGMP but not 3\',5\'-cAMP/cGMP phosphodiesterase activity and suppresses cell death activity of
TIRs in Nb. Our study identifies a family of 2\',3\'-cAMP/cGMP synthetases and establishes a critical role for them in plant immune responses.