Collaborative Research: Protein Arginine Methylation

合作研究：蛋白质精氨酸甲基化

• 批准号: 1412358
• 负责人: Orlando Acevedo
• 金额: $ 15万
• 依托单位: Auburn University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1412358&HistoricalAwards=false
• 关键词: Collaborative; Research; Protein; Arginine; Methylation

The addition of one or more specific markers to proteins by enzymes known as protein arginine methyltransferases (PRMTs) allows cells to adapt to their ever-changing environments. Biological pathways responsible for development, the response to hormones and viruses, cancer and cardiovascular disease are all impacted by exactly how PRMTs carry out their additions to protein targets. The studies will characterize how the individual members of the PRMT family dictate very specific product formation, for example, one versus two additions, in order to direct the result that is required in the cell. The proposed strategy will integrate both computational modeling and ?at-the-bench? biochemical experiments to reveal just how product formation takes place for two members of the PRMT family. The results of these studies will provide foundational information that is required for novel inhibitor development, as well as allow for an understanding of the sophisticated role PRMTs play in cellular signaling. The studies will provide cross training for students in both computational and wet biochemistry experimental strategies, as well as provide the opportunity for undergraduates to receive on-the-job training in the lab, preparing them for the STEM workforce. With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Joan Hevel and Dr. Orlando Acevedo to characterize the mechanism of protein arginine monomethylation versus dimethylation using advanced computational and biophysical techniques. The role of sterics, dynamics, and mode of substrate binding in determining which of two different methylation products the protein arginine methyltransferases form will be determined. Information from this study will provide new insight into the sophisticated control of product formation that is required to maintain appropriate patterns of signaling in cells.

通过蛋白质精氨酸甲基转移酶 (PRMT) 向蛋白质添加一种或多种特定标记，使细胞能够适应不断变化的环境。 负责发育、对激素和病毒的反应、癌症和心血管疾病的生物途径都受到 PRMT 如何添加蛋白质靶标的影响。 这些研究将描述 PRMT 家族的各个成员如何决定非常具体的产物形成，例如，一种或两种添加，以指导细胞中所需的结果。 所提出的策略将整合计算建模和“实验台”？生化实验揭示了 PRMT 家族的两个成员的产物形成过程。 这些研究的结果将提供新型抑制剂开发所需的基础信息，并有助于了解 PRMT 在细胞信号传导中发挥的复杂作用。 这些研究将为学生提供计算和湿生物化学实验策略方面的交叉培训，并为本科生提供在实验室接受在职培训的机会，为他们成为 STEM 劳动力做好准备。凭借该奖项，化学部的生命过程化学项目将资助 Joan Hevel 博士和 Orlando Acevedo 博士使用先进的计算和生物物理技术来表征蛋白质精氨酸单甲基化与二甲基化的机制。 将确定空间、动力学和底物结合模式在确定蛋白质精氨酸甲基转移酶形成两种不同甲基化产物中的哪一种中的作用。 这项研究的信息将为维持细胞内适当的信号传导模式所需的产物形成的复杂控制提供新的见解。