PDF(Pubmed)
Abstract：
Plant hormone-related transcription factors (TFs) are key regulators of plant development, responses to environmental stress such as climate changes, pathogens, and pests. These TFs often function as families that exhibit genetic redundancy in higher plants, and are affected by complex crosstalk mechanisms between different plant hormones. These properties make it difficult to analyze and control them in many cases. In this study, we introduced a chemical inhibitor to manipulate plant hormone-related TFs, focusing on the jasmonate (JA) and ethylene (ET) signaling pathways, with the key TFs MYC2/3/4 and EIN3/EIL1. This study revealed that JAZ10CMID, the binding domain of the repressor involved in the desensitization of both TFs, is an intrinsically disordered region in the absence of binding partners. Chemical inhibitors have been designed based on this interaction to selectively inhibit MYC TFs while leaving EIN3/EIL1 unaffected. This peptide inhibitor effectively disrupts MYC-mediated responses while activating EIN3-mediated responses and successfully uncouples the crosstalk between JA and ET signaling in Arabidopsis thaliana. Furthermore, the designed peptide inhibitor was also shown to selectively inhibit the activity of MpMYC, an ortholog of AtMYC in Marchantia polymorpha, demonstrating its applicability across different plant species. This underscores the potential of using peptide inhibitors for specific TFs to elucidate hormone crosstalk mechanisms in non-model plants without genetic manipulation. Such a design concept for chemical fixation of the disordered structure is expected to limit the original multiple binding partners and provide useful chemical tools in chemical biology research.
摘要：
植物激素相关转录因子(TFs)是植物发育的关键调控因子,对气候变化等环境压力的反应，病原体,和害虫。这些TFs通常在高等植物中表现出遗传冗余的家族，并且受到不同植物激素之间复杂的串扰机制的影响。这些性质使得在许多情况下难以分析和控制它们。在这项研究中,我们引入了一种化学抑制剂来操纵植物激素相关的TFs，关注茉莉酸（JA）和乙烯（ET）信号通路，与关键TFsMYC2/3/4和EIN3/EIL1。这项研究表明，JAZ10CMID，参与两种TFs脱敏的阻遏物的结合域，是在没有结合伴侣的情况下的内在无序区域。已经基于这种相互作用设计了化学抑制剂以选择性地抑制MYCTF,同时使EIN3/EIL1不受影响。这种肽抑制剂有效地破坏MYC介导的反应，同时激活EIN3介导的反应，并成功地解开拟南芥中JA和ET信号之间的串扰。此外，设计的肽抑制剂还显示选择性地抑制MpMYC的活性，Marchantiapolymora中AtMYC的直系同源物，证明了它在不同植物物种中的适用性。这强调了将肽抑制剂用于特定TFs以阐明非模型植物中的激素串扰机制而无需遗传操作的潜力。这种用于无序结构的化学固定的设计概念有望限制原始的多个结合伴侣，并在化学生物学研究中提供有用的化学工具。
