Structural basis for repressor-activator transitions in response to the plant defense hormone, jasmonic acid

当植物被昆虫捕食或被微生物病原体感染时，它们会产生激素作为信号，让植物进行防御。这种防御通常包括开启或激活有益的基因，帮助植物在损害中存活下来，然后在危险减弱后关闭或抑制这些基因。这项研究旨在了解这些基因如何从“关闭”转变为“打开”的分子细节。了解详细的机制可能对农业具有广泛的重要意义，因为它为基因操作和作物植物的开发提供了基础，从而优化了防御和生长。该项目将为来自当地社区学院的客座国际研究生和本科生提供研究培训机会，从而有助于培养未来的科学人才。此外，通过参与动手研究经验，高中教师将提高他们沟通科学过程的能力，并使学生参与有意义的科学学习。本研究的重点是植物防御激素茉莉酸。在健康的植物中，茉莉酸反应基因是由一种多蛋白复合物结合的，该复合物由一种叫做JAZ的抑制因子、一种叫做MYC的转录激活因子和一组其他蛋白质组成。在没有茉莉酸盐的情况下，JAZ抑制因子抑制MYC激活因子，基因在转录上沉默或关闭。为了应对食草昆虫和许多微生物病原体的伤害，茉莉酸产生并通过诱导蛋白酶体降解JAZ抑制因子来激活这些基因，从而减轻MYC的抑制，MYC通过激活转录来激活这些基因。参与这种从抑制状态到活性状态转变的许多蛋白质的分子细节和所起的作用在很大程度上是未知的。该项目旨在发现参与茉莉酸信号传导的大型多蛋白复合物是如何组装和调节的。方法将包括x射线晶体学、电子显微镜、生物化学、生物物理学、植物分析和细胞信号重建的结合。由于许多信号级联导致从抑制到活跃的基因表达的转变，因此该结果可以作为发现并最终操纵负责调节的蛋白复合物的范例。该奖项由生物科学理事会分子生物科学部的遗传机制和分子生物物理学项目共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

When plants are wounded by insect feeding or infected by microbial pathogens, they respond by producing hormones that function as signals to allow the plant to mount a defense. Often the defense involves turning on, or activating, beneficial genes that help the plant survive the damage and then turning off, or repressing, those genes once the danger wanes. This research seeks to understand the molecular details of how these genes transition from "off" to "on". Knowledge of the detailed mechanism could be broadly important for agriculture by providing a foundation for genetic manipulation and development of crop plants optimized for defense and growth. This project will offer research training opportunities to guest international graduate students and undergraduates from from a local community college, thereby contributing to the preparation of the future scientific workforce. In addition, through participation in hands-on research experiences, high school teachers will improve their ability to communicate the scientific process and engage their students in meaningful science learning. This research is focused on the plant defense hormone jasmonate. In healthy plants, jasmonate-responsive genes are bound by a multi-protein complex composed of a repressor called JAZ, a transcriptional activator called MYC, and a group of other proteins. In the absence of jasmonate, the JAZ repressor inhibits the MYC activator, and the genes are transcriptionally silent, or off. In response to damage from herbivorous insects and many microbial pathogens, jasmonate is produced and turns on these genes by inducing the proteasomal degradation of the JAZ repressor, thereby relieving inhibition of MYC, which turns on the genes by activating transcription. The molecular details and the roles played by the many proteins that participate in this transition from repressed to active state are largely unknown. This project seeks to discover how the large multi-protein complexes involved in jasmonate signaling are assembled and regulated. Approaches will include a combination of X-ray crystallography, electron microscopy, biochemical, biophysical, and in planta analyses, and in cell signaling reconstitution. Because many signaling cascades result in transitions from repressed to active gene expression, the results could serve as a paradigm for discovering, and eventually manipulating, the responsible regulatory protein complexes. This award was co-funded by the Genetic Mechanisms and the Molecular Biophysics Programs in the Division of Molecular Biosciences in the Directorate for Biological Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.