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

响应植物防御激素茉莉酸的阻遏物-激活物转变的结构基础

• 批准号: 1922846
• 负责人: Karsten Melcher
• 金额: $ 120万
• 依托单位: Van Andel Research Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1922846&HistoricalAwards=false
• 关键词: Structural; basis; repressor; activator; transitions

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.

当植物因昆虫进食而受伤或被微生物病原体感染时，它们会通过产生激素来做出反应，这些激素充当信号，使植物能够进行防御。 通常，防御涉及打开或激活有助于植物在损害中生存的有益基因，然后在危险减弱时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“开启”的分子细节。 了解详细机制可能对农业具有广泛的重要意义，因为它为遗传操纵和开发针对防御和生长进行优化的作物植物提供了基础。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，从而为未来科学劳动力的准备做出贡献。此外，通过参与实践研究经验，高中教师将提高他们交流科学过程并让学生参与有意义的科学学习的能力。 这项研究的重点是植物防御激素茉莉酸。 在健康植物中，茉莉酸反应基因与多蛋白复合物结合，该多蛋白复合物由名为 JAZ 的阻遏蛋白、名为 MYC 的转录激活蛋白和一组其他蛋白组成。 在缺乏茉莉酸的情况下，JAZ 阻遏蛋白会抑制 MYC 激活蛋白，并且基因转录沉默或关闭。 为了应对食草昆虫和许多微生物病原体的损害，茉莉酸会产生，并通过诱导 JAZ 阻遏物的蛋白酶体降解来打开这些基因，从而解除 MYC 的抑制，而 MYC 通过激活转录来打开这些基因。 参与从抑制状态到活跃状态转变的许多蛋白质的分子细节和所发挥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、植物分析和细胞信号重建的组合。由于许多信号级联会导致基因表达从抑制向活跃的转变，因此这些结果可以作为发现并最终操纵负责的调节蛋白复合物的范例。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 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。