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.

当植物受到昆虫喂养或被微生物病原体感染的伤害时，它们通过产生充当信号的激素来做出反应，以使植物施加防御。 防御通常涉及开启或激活有益的基因，这些基因有助于植物造成损害，然后将这些基因关闭或抑制一旦危险减弱。 这项研究试图了解这些基因如何从“ OFF”到“ ON”的分子细节。 通过为农业的基础提供了针对国防和生长优化的作物植物的基础，对详细机制的了解对于农业可能至关重要。该项目将为来宾国际研究生和本科生提供研究培训机会，从当地一所社区学院提供，从而为未来的科学劳动力做准备。此外，通过参与动手研究经验，高中教师将提高他们传达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jasmonate。 在健康的植物中，贾斯对响应基因由一个多蛋白质复合物结合，该复合物由称为MYC的转录激活剂JAZ和其他一组其他蛋白质组成。 在缺乏jasmonate的情况下，JAZ抑制剂抑制了MYC激活剂，并且基因在转录上是无声的，或者是OFF的。 为了响应草食性昆虫和许多微生物病原体的损害，产生了贾斯酸盐，并通过诱导JAZ抑制剂的蛋白酶体降解来转化这些基因，从而缓解了对Myc的抑制，从而通过激活转录来打开基因。 从抑制状态过渡到活跃状态的许多蛋白质的分子细节和作用在很大程度上是未知的。 该项目旨在发现如何组装和调节参与茉莉酸酯信号的大型多蛋白质复合物。 方法将包括X射线晶体学，电子显微镜，生化，生物物理和植物分析以及细胞信号重构的组合。由于许多信号传导级联反应导致从抑制至活性基因表达的过渡，因此结果可以作为发现并最终操纵负责任调节蛋白复合物的范式。该奖项是由遗传机制和分子生物物理学计划共同资助的，该奖项在生物科学局的分子生物科学局中。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来支持的。