Role of posttranslational modifications in controlling the specificity of response regulation

生物体基因中编码的信息最终被解码为蛋白质，这些蛋白质作为关键酶、细胞、转运体或受体的组成部分，执行几乎所有的细胞功能。蛋白质由20种不同的氨基酸组成，其序列由基因的核苷酸序列决定。这些氨基酸中的大多数在翻译后可以共价修饰，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)是自然界放大基因组中编码的信息的方式，为调节生物体的发育、生理和生存提供动态、灵活和潜在可逆的机制。对于多功能蛋白质来说，特定的PTM可能与明确的蛋白质功能有关。因此，对生物体‘PTM密码’的全面解读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在特定背景下的PTMS如何决定蛋白质在调节不同反应中的作用的知识方面的主要空白，而且还将大大有助于阐明影响关键农艺性状的植物信号机制。因此，除了促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当今困扰我们的世界的问题：利用有限的资源和不利的环境产生更高的产量。这项工作还将包括培训一名技术员、一名多学科领域的博士后科学家和指导本科生。这项研究将通过一系列动手实验和互动演示，帮助促进高中生和普通公众对植物科学的理解。该项目旨在确定单一蛋白--拟南芥异三聚体G-α蛋白(GPA1)是否存在多种上下文相关的蛋白形式，并将它们与GPA1调节的特定功能联系起来。对生物体翻译后修饰依赖的蛋白质编码的全面解释对于理解基因与表型之间的联系至关重要。这项研究解决了与PTMS的作用相关的一些最基本的问题，例如(I)特定的PTMS如何影响蛋白质的核心性质，(Ii)蛋白质的PTMS的有机体水平和上下文特定的影响，以及(Iii)这种特异性是如何实现的。这项研究的成功完成不仅将填补我们在蛋白质PTM调控作用方面的主要知识空白，而且还将产生一个适用于其他植物(和后生动物)的知识库，在这些知识库中，由于系统的复杂性，类似的分析是不可能的。它还将有助于微调与农业相关的植物G蛋白信号机制，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影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.