Functional characterization of the enzyme dipeptide interaction network and its role in the regulation of Arabidopsis carbon metabolism

酶二肽相互作用网络的功能表征及其在拟南芥碳代谢调控中的作用

• 批准号: 2226270
• 负责人: Aleksandra Skirycz
• 金额: $ 47.13万
• 依托单位: Boyce Thompson Institute Plant Research
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2226270&HistoricalAwards=false
• 关键词: Functional; characterization; enzyme; dipeptide; interaction

Metabolism drives the life-sustaining chemical reactions that provide energy and building blocks for plant growth and function. The goal of this project is to investigate how a class of small-molecule compounds called dipeptides control the activity of the central carbon metabolism of plants. This research may lead to innovation in the form of dipeptide-based strategies for improving plant fitness and perhaps generate knowledge that can be used in human and animal health. This project will provide research training for high school students, undergraduate students and post-doctoral associates.Due to its rapid and reversible nature, small-molecule regulation of key enzymatic activities is vital to controlling metabolic fluxes. Systematic identification of regulatory metabolite-enzyme interactions remains one of the grand challenges in metabolism research. This research aims to systematically characterize the newly discovered enzyme-dipeptide interaction network and its role in regulating central carbon metabolism in the model plant Arabidopsis thaliana. To elucidate the metabolic consequences of the studied enzyme-dipeptide interactions, the research will exploit a combination of in vitro bimolecular binding assays, characterization of enzymatic activities, comprehensive metabolomic analysis of steady-state metabolite levels, and 13C metabolic flux analysis after dipeptide treatments. The results of these assays will be overlaid with dipeptide accumulation patterns to demonstrate the physiological relevance of the identified interactions. The basic knowledge accrued through this project will shed light on one of the central questions in biology: how organisms regulate their metabolism as they adapt to the environment. The research will characterize a hidden world of largely uninvestigated enzyme-dipeptide interactions, as well as their role in the critical yet poorly understood regulatory nexus of protein degradation and metabolism.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.

新陈代谢驱动着维持生命的化学反应，为植物的生长和功能提供能量和基石。该项目的目标是研究一类称为二肽的小分子化合物如何控制植物中心碳代谢的活性。这项研究可能会导致以二肽为基础的改善植物适应性的策略形式的创新，并可能产生可用于人类和动物健康的知识。该项目将为高中生、本科生和博士后提供研究培训。由于其快速和可逆的性质，关键酶活性的小分子调节对于控制代谢通量至关重要。系统地鉴定调节性代谢物-酶相互作用仍然是代谢研究中的重大挑战之一。本研究旨在系统地研究新发现的酶-二肽相互作用网络及其在模式植物拟南芥中心碳代谢调控中的作用。为了阐明所研究的酶-二肽相互作用的代谢后果，该研究将利用体外双分子结合试验、酶活性表征、稳态代谢物水平的综合代谢组学分析和二肽治疗后的13 C代谢通量分析的组合。这些试验的结果将与二肽蓄积模式重叠，以证明已鉴别相互作用的生理相关性。通过这个项目积累的基本知识将阐明生物学的一个核心问题：生物体如何调节它们的新陈代谢，以适应环境。该研究将描述一个隐藏的世界，主要是未经调查的酶-二肽相互作用，以及它们在蛋白质降解和代谢的关键但知之甚少的调控关系中的作用。该奖项反映了NSF的法定使命，并被认为值得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来支持。

项目成果

Protein interactome of 3′,5′‐cAMP reveals its role in regulating the actin cytoskeleton

3-,5-2-cAMP蛋白相互作用组揭示其调节肌动蛋白细胞骨架的作用

• DOI: 10.1111/tpj.16313
• 发表时间: 2023
• 期刊: The Plant Journal
• 作者: Figueroa, Nicolás E.;Franz, Peter;Luzarowski, Marcin;Martinez‐Seidel, Federico;Moreno, Juan C.;Childs, Dorothee;Ziemblicka, Aleksandra;Sampathkumar, Arun;Andersen, Tonni Grube;Tsiavaliaris, Georgios
• 通讯作者: Tsiavaliaris, Georgios