Protein Arginine Methylation by PRMT1

PRMT1 使蛋白质精氨酸甲基化

• 批准号: 0920776
• 负责人: Joan Hevel
• 金额: $ 57.52万
• 依托单位: Utah State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0920776&HistoricalAwards=false
• 关键词: Protein; Arginine; Methylation; PRMT1

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).In order to increase the functionality of the small number of proteins encoded by mammalian genomes, proteins are often decorated with a variety of chemical appendages that alter the behavior of the protein. Having the ability to alter proteins in this way is a hallmark feature of any cell's ability to adapt its response to the environment. In the first aim, this project will use novel methods and mechanistic approaches to clarify how one of these enzymes, called protein arginine methyltransferase 1 (PRMT1), recognizes its target proteins and how it performs the chemical transformation (protein arginine methylation). In particular the project will study a novel regulatory mechanism to control how PRMT1 performs its job inside the cell. In the second aim, the project will determine the mechanistic role of a portion of PRMT1 called the tail. Of the 11 different kinds of PRMTs, the tails on each of the enzymes are very different; suggesting that the tail may be involved in specifying which proteins should be targeted by each PRMT. The results will provide a framework for studying the other PRMT enzymes. These studies will be a much needed counterpart to the cell biological approaches that predominate in the field of PRMTs. Broader Impacts The inclusion of undergraduates in the research endeavor will be a primary focus of the PI. In addition to undergraduates mentored personally by the PI, portions of the research will be conducted by students in the senior-level undergraduate Biochemistry laboratory course. Web-based reporting will allow students to track the progress of the research providing context for the experiment. These efforts will help to transform the outdated laboratory course into a more interactive and novel experience for the students. The PI will continue to participate in an Undergraduate Research Program to reach students at institutions that do not have internal research opportunities. As a form of outreach to K-12 education, the PI will continue to participate in the development and implementation of the Department's high school summer research program, from which students will be selected and incorporated into the multi-disciplinary research team over the duration of the project. In summary, the PI will integrate the training of graduate, undergraduate, and high school students with high level research efforts that will answer fundamental questions about the biochemistry of PRMT1.

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。为了增加哺乳动物基因组编码的少数蛋白质的功能，蛋白质通常被装饰以各种化学附属物，以改变蛋白质的行为。以这种方式改变蛋白质的能力是任何细胞适应环境的能力的一个标志性特征。在第一个目标中，该项目将使用新的方法和机制方法来阐明其中一种称为蛋白质精氨酸甲基转移酶1 （PRMT1）的酶如何识别其靶蛋白以及它如何进行化学转化（蛋白质精氨酸甲基化）。特别是，该项目将研究一种新的调节机制来控制PRMT1如何在细胞内执行其工作。在第二个目标中，该项目将确定PRMT1中称为尾部的部分的机制作用。在11种不同的prmt中，每种酶的尾部都非常不同；这表明尾巴可能参与指定每个PRMT应该靶向哪些蛋白质。该结果将为其他PRMT酶的研究提供一个框架。这些研究将成为在PRMTs领域占主导地位的细胞生物学方法的一个非常需要的对应物。更广泛的影响将本科生纳入研究努力将是PI的主要焦点。除了由PI亲自指导的本科生外，部分研究将由高年级本科生生物化学实验课程的学生进行。基于网络的报告将允许学生跟踪研究的进展，为实验提供背景。这些努力将有助于将过时的实验课程转变为更具互动性和新颖的体验。PI将继续参与本科生研究计划，以接触没有内部研究机会的机构的学生。作为延伸到K-12教育的一种形式，PI将继续参与该部门的高中暑期研究计划的制定和实施，从中选择学生并在项目期间纳入多学科研究团队。总之，该项目将把研究生、本科生和高中生的培训与高水平的研究工作结合起来，这些研究工作将回答有关PRMT1生物化学的基本问题。