Elucidating the functions of RPD3/HDA1-like lysine deacetylases in Arabidopsis thaliana

阐明拟南芥中 RPD3/HDA1 样赖氨酸脱乙酰酶的功能

• 批准号: 398145771
• 负责人: Professorin Dr. Iris Finkemeier
• 金额: --
• 依托单位: Arbeitsgruppe Plant Physiology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/398145771?language=en
• 关键词: Elucidating; functions; RPD3; HDA1; like

Reversible acetylation of the ε-amino group of lysine has recently emerged as an ubiquitous post-translational modification controlling many important cellular functions beyond transcription. It is a conserved modification occurring on proteins of both, prokaryotes and eukaryotes, indicating its universal importance for life. The identification of lysine acetylation sites on many metabolic enzymes was a first step to uncover its physiological role in metabolism. Lysine acetylation is catalysed by the antagonistic action of lysine acetyltransferases and lysine deacetylases. Lysine deacetylases (KDACs) have central functions in regulating stress defenses and development in plants, but their action was mainly investigated in the context of histones thus far, and their versatility in molecular activities is still largely unexplored. This project aims at a comprehensive investigation on the molecular functions of Arabidopsis RPD3/HDA1-like KDACs to uncover new functions and target proteins connected to plant stress physiology and development. This project will employ a sophisticated biochemical toolbox for dissecting novel KDAC functions in plants. The toolbox will include activity-based probes for the pull-down of active KDACs from tissues and analysed by quantitative mass spectrometry, large-scale acetylome profiling of KDAC mutants, and testing new peptide-based acyl-lysine substrates to determine their enzymatic properties. Taken together these approaches shall uncover novel KDAC functions important for the integration of stress responses and development in plants.

赖氨酸的ε-氨基的可逆乙酰化最近已成为一种普遍存在的翻译后修饰，控制转录以外的许多重要细胞功能。它是一种发生在原核生物和真核生物蛋白质上的保守修饰，表明其对生命的普遍重要性。许多代谢酶上赖氨酸乙酰化位点的鉴定是揭示其在代谢中生理作用的第一步。赖氨酸乙酰化由赖氨酸乙酰转移酶和赖氨酸脱乙酰酶的拮抗作用催化。赖氨酸脱乙酰基酶（KDAC）在调节植物的逆境防御和发育中具有重要的功能，但迄今为止，它们的作用主要是在组蛋白的背景下研究的，其分子活性的多样性在很大程度上尚未被探索。本项目旨在全面研究拟南芥RPD 3/HDA 1-like KDAC的分子功能，以发现与植物胁迫生理和发育相关的新功能和靶蛋白。该项目将采用先进的生物化学工具箱来解剖植物中的新KDAC功能。该工具箱将包括基于活性的探针，用于从组织中拉下活性KDAC，并通过定量质谱法进行分析，KDAC突变体的大规模乙酰组分析，以及测试新的基于肽的酰基赖氨酸底物以确定其酶特性。总之，这些方法将揭示新的KDAC功能的重要整合胁迫反应和发展的植物。