START Lipid/Sterol Binding Domains in Homeodomain Transcription Factors from Plants

START 植物同源域转录因子中的脂质/甾醇结合域

• 批准号: 1616818
• 负责人: Kathrin Schrick
• 金额: $ 32.1万
• 依托单位: Kansas State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1616818&HistoricalAwards=false
• 关键词: START; Lipid; Sterol; Binding; Domains

In all multicellular organisms, key regulatory proteins orchestrate the developmental program that defines how specific cell types and tissues are formed. This project will investigate how the regulatory proteins themselves are controlled by interactions with fat molecules. Plants produce a multitude of different fat molecules and other natural products whose molecular functions are not yet understood. The regulatory proteins and fats to be studied in this project are suspected to participate in plant growth control, along with traits that contribute to drought tolerance. Broader impacts of this research will include training of a postdoctoral scholar and several undergraduate students through programs for McNair Scholars, Kansas Louis Stokes Alliance for Minority Participation, and the REU program on Ecology and Evolution in Changing Environments. Public outreach will be accomplished through an educational workshop for teenage girls with interests in STEM careers. The information gained from this research will foster discovery of renewable and sustainable plant-derived products. Interactions between lipid metabolites and proteins are dynamic in all life forms, yet the full extent and biological significance of these interactions is underexplored. Steroidogenic Acute Regulatory (StAR) protein-related lipid Transfer (START) domains belong to an ancient clan of protein motifs characterized by binding to hydrophobic ligands. In plants, START domains occur in homeodomain leucine-zipper (HD-Zip) transcription factors that are master regulators of cell-type differentiation during development. This project addresses the hypothesis that the START domain controls transcription factor activity via ligand binding to a lipid metabolite, linking cell metabolism to gene expression. The overall goal is to identify the natural ligands of HD-Zip-derived START domains. This research will utilize the Arabidopsis model system focusing on class IV HD-Zip transcription factors that are critical for differentiation of the epidermis. Candidate ligands will be identified by protein-metabolite immunoisolation from plant tissues followed by mass spectrometry. Biochemical approaches will be utilized to validate and further characterize protein-metabolite interactions. This project is poised to uncover novel mechanistic insights in understanding the dynamic interplay between metabolic pathways and the regulation of gene expression in the eukaryotes.This project is funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences.

在所有的多细胞生物中，关键的调节蛋白协调了发育程序，定义了特定的细胞类型和组织是如何形成的。 该项目将研究调节蛋白本身如何通过与脂肪分子的相互作用来控制。植物产生多种不同的脂肪分子和其他天然产物，其分子功能尚未了解。在这个项目中要研究的调节蛋白和脂肪被怀疑参与植物生长控制，沿着有助于耐旱性的性状。这项研究的更广泛的影响将包括通过麦克奈尔学者，堪萨斯路易斯斯托克斯少数民族参与联盟和REU生态学和进化在不断变化的环境中的程序的博士后学者和几个本科生的培训。将通过为对STEM职业感兴趣的少女举办教育讲习班来实现公共宣传。从这项研究中获得的信息将促进可再生和可持续植物衍生产品的发现。脂质代谢物和蛋白质之间的相互作用在所有生命形式中都是动态的，但这些相互作用的完整程度和生物学意义尚未得到充分研究。类固醇生成急性调节（星星）蛋白相关脂质转移（START）结构域属于一个古老的蛋白质基序家族，其特征在于与疏水配体结合。在植物中，START结构域存在于同源结构域亮氨酸拉链（HD-Zip）转录因子中，这些转录因子是发育过程中细胞类型分化的主要调节因子。该项目解决了START结构域通过与脂质代谢物结合的配体控制转录因子活性，将细胞代谢与基因表达联系起来的假设。总体目标是鉴定HD-Zip衍生的START结构域的天然配体。这项研究将利用拟南芥模型系统，重点是IV类HD-Zip转录因子，这是表皮分化的关键。候选配体将通过从植物组织中进行蛋白质代谢物免疫分离，然后进行质谱分析来鉴定。生物化学方法将用于验证和进一步表征蛋白质-代谢物相互作用。本项目由分子和细胞生物科学部遗传机制计划资助，旨在揭示真核生物中代谢途径和基因表达调控之间的动态相互作用。