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Role of posttranslational modifications in controlling the specificity of response regulation

翻译后修饰在控制反应调节特异性中的作用

基本信息

批准号：
2207012
负责人：
Sona Pandey
金额：
$ 72.01万
依托单位：
Donald Danforth Plant Science Center
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-15 至 2025-06-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2207012&HistoricalAwards=false
关键词：
Role posttranslational modifications controlling specificity

项目摘要

The information encoded in the genes of an organism is ultimately decoded as proteins, which by acting as key enzymes, building blocks of a cell, transporters, or receptors, perform almost all cellular functions. Proteins are made of a permutation of 20 distinct amino acids, the sequence of which is determined by the nucleotide sequence of genes. Most of these amino acids can be covalently modified after their translation, resulting in multiple, unique proteoforms of a single protein with distinct function. The post-translational modifications (PTMs) are thus nature’s way of amplifying the information encoded in the genome to provide dynamic, flexible and potentially reversible mechanisms for regulating an organism’s development, physiology and survival. For multi-functional proteins, specific PTMs may associate with explicit protein function. Therefore, comprehensive interpretation of the ‘PTM code’ of an organism is critical to understand the gene to function link. Successful completion of this research will not only fill major gaps in our knowledge of how context-specific PTMs dictate the roles of a protein in regulation of distinct responses, but will also add significantly to elucidation of plant signaling mechanisms, which affect key agronomical traits. Therefore, in addition to advancing our fundamental understanding of a complex biological concept, this research will also apply broadly to the problems that plague our world today: generating higher yield with limited resources and unfavorable environments. The work will also involve the training of a technician, a postdoctoral scientist in a multidisciplinary field and mentoring of undergraduate students. The research will help promote an understanding of plant science to the high school students and general public via a series of hands on experiments and interactive presentations. This project aims to determine the existence of multiple, context-dependent proteoforms of a single protein, the Arabidopsis heterotrimeric Gα protein (GPA1) critical to G-protein signaling, and connect them to specific GPA1-regulated functions. Comprehensive interpretation of the post-translational modification-dependent ‘protein code’ of an organism is critical to understand the genotype to phenotype link. This research addresses some of the most fundamental questions related to the roles of PTMs such as (i) how specific PTMs affect the core properties of a protein, (ii) what are the organism-level, context-specific effects of PTMs of a protein, and (iii) how this specificity is achieved. Successful completion of this research will not only fill major gaps in our knowledge of regulatory roles of protein PTMs, but will also generate a knowledge base suitable for other plants (and metazoans), where similar analyses are not possible due to complexity of the system. It will also help fine-tune the plant G-protein signaling mechanisms of agricultural relevance because naturally occurring or engineered changes in G-proteins have profound effects on plant architecture, stress responses and yield.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.

编码在生物体基因中的信息最终被解码为蛋白质，蛋白质作为关键酶、细胞的构建模块、转运蛋白或受体，执行几乎所有的细胞功能。蛋白质由20种不同的氨基酸排列而成，其序列由基因的核苷酸序列决定。这些氨基酸中的大多数可以在翻译后被共价修饰，从而产生具有不同功能的单一蛋白质的多种独特的蛋白质形式。因此，翻译后修饰（PTM）是放大基因组中编码的信息的自然方式，以提供用于调节生物体的发育、生理和存活的动态、灵活和潜在可逆的机制。对于多功能蛋白质，特定的PTM可能与明确的蛋白质功能相关。因此，全面解释生物体的“PTM密码”对于理解基因与功能的联系至关重要。这项研究的成功完成不仅将填补我们对特定环境的PTM如何决定蛋白质在调节不同反应中的作用的知识的主要空白，而且还将显著增加对影响关键农艺性状的植物信号传导机制的阐明。因此，除了推进我们对复杂生物学概念的基本理解外，这项研究还将广泛应用于困扰我们当今世界的问题：以有限的资源和不利的环境产生更高的产量。这项工作还将涉及培训一名技术员、一名多学科领域的博士后科学家和指导本科生。这项研究将有助于促进植物科学的理解，高中学生和公众通过一系列的动手实验和互动演示。该项目旨在确定单个蛋白质（拟南芥异源三聚体Gα蛋白（GPA1））的多个上下文依赖性蛋白质型的存在，并将它们与特定的GPA1调节功能联系起来。对生物体翻译后修饰依赖的“蛋白质密码”的全面解释对于理解基因型与表型的联系至关重要。这项研究解决了一些与PTM作用相关的最基本的问题，例如（i）特定的PTM如何影响蛋白质的核心特性，（ii）蛋白质的PTM的生物体水平，上下文特异性效应是什么，以及（iii）如何实现这种特异性。这项研究的成功完成不仅将填补我们对蛋白质PTM的调控作用的知识的主要空白，而且还将产生适合于其他植物（和后生动物）的知识库，其中由于系统的复杂性而不可能进行类似的分析。它还将有助于微调与农业相关的植物G蛋白信号传导机制，因为G蛋白的自然发生或工程变化对植物结构，胁迫反应和产量有深远的影响。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。