Ye Yajin, Zhou Lijuan, Liu Xue, Liu Hao, Li Deqiang, Cao Minjie, Chen Haifeng, Xu Lin, Zhu Jian-Kang, Zhao Yang
Institute of Plant Physiology and Ecology (Y.-J.Y., L.-J.Z., D.-Q.L., L.X., Y.Z.) and Shanghai Center for Plant Stress Biology (X.L., M.-J.C., J.-K.Z.), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
University of the Chinese Academy of Sciences, Beijing 100000, China (Y.-J.Y., L.-J.Z., D.-Q.L.).
Plant Physiol. 2017 Apr;173(4):2356-2369. doi: 10.1104/pp.16.01862. Epub 2017 Feb 13.
Abscisic acid (ABA), the most important stress-induced phytohormone, regulates seed dormancy, germination, plant senescence, and the abiotic stress response. ABA signaling is repressed by group A type 2C protein phosphatases (PP2Cs), and then ABA binds to its receptor of the ACTIN RESISTANCE1 (PYR1), PYR1-LIKE (PYL), and REGULATORY COMPONENTS OF ABA RECEPTORS (RCAR) family, which, in turn, inhibits PP2Cs and activates downstream ABA signaling. The agonist/antagonist of ABA receptors have the potential to reveal the ABA signaling machinery and to become lead compounds for agrochemicals; however, until now, no broad-spectrum antagonists of ABA receptors blocking all PYR/PYL-PP2C interactions have been identified. Here, using chemical genetics screenings, we identified ABA ANTAGONIST1 (AA1), the first broad-spectrum antagonist of ABA receptors in Arabidopsis (). Physiological analyses revealed that AA1 is sufficiently active to block ABA signaling. AA1 interfered with all the PYR/PYL-HAB1 interactions, and the diminished PYR/PYL-HAB1 interactions, in turn, restored the activity of HAB1. AA1 binds to all 13 members. Molecular dockings, the non-AA1-bound PYL2 variant, and competitive binding assays demonstrated that AA1 enters into the ligand-binding pocket of PYL2. Using AA1, we tested the genetic relationships of ABA receptors with other core components of ABA signaling, demonstrating that AA1 is a powerful tool with which to sidestep this genetic redundancy of PYR/PYLs. In addition, the application of AA1 delays leaf senescence. Thus, our study developed an efficient broad-spectrum antagonist of ABA receptors and demonstrated that plant senescence can be chemically controlled through AA1, with a simple and easy-to-synthesize structure, allowing its availability and utility as a chemical probe synthesized in large quantities, indicating its potential application in agriculture.
脱落酸（ABA）是最重要的应激诱导植物激素，它调节种子休眠、萌发、植物衰老以及非生物胁迫响应。ABA信号传导受到A类2C型蛋白磷酸酶（PP2C）的抑制，然后ABA与其ACTIN RESISTANCE1（PYR1）、PYR1-LIKE（PYL）和ABA受体调节成分（RCAR）家族的受体结合，进而抑制PP2C并激活下游ABA信号传导。ABA受体的激动剂/拮抗剂有可能揭示ABA信号传导机制，并成为农用化学品的先导化合物；然而，到目前为止，尚未鉴定出能阻断所有PYR/PYL-PP2C相互作用的ABA受体广谱拮抗剂。在这里，我们通过化学遗传学筛选，鉴定出了ABA拮抗剂1（AA1），它是拟南芥中首个ABA受体广谱拮抗剂。生理分析表明，AA1具有足够的活性来阻断ABA信号传导。AA1干扰了所有PYR/PYL-HAB1的相互作用，而PYR/PYL-HAB1相互作用的减弱反过来又恢复了HAB1的活性。AA1与所有13个成员结合。分子对接、未结合AA1的PYL2变体和竞争性结合试验表明，AA1进入了PYL2的配体结合口袋。使用AA1，我们测试了ABA受体与ABA信号传导其他核心成分之间的遗传关系，证明AA1是一个强大的工具，可避开PYR/PYLs的这种遗传冗余。此外，AA1的应用延缓了叶片衰老。因此，我们的研究开发出了一种高效的ABA受体广谱拮抗剂，并证明可以通过结构简单且易于合成的AA1对植物衰老进行化学控制，这使得它能够作为一种可大量合成的化学探针使用，表明了其在农业中的潜在应用价值。
