RUI: Domain-Domain and Protein-Protein Interactions in Reactive Oxygen Species

RUI：活性氧中的域-域和蛋白质-蛋白质相互作用

• 批准号: 1608484
• 负责人: Chin-Chuan Wei
• 金额: $ 21.38万
• 依托单位: Southern Illinois University at Edwardsville
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1608484&HistoricalAwards=false
• 关键词: RUI; Domain; Protein; Interactions; Reactive

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Chin-Chuan Wei from Southern Illinois University Edwardsville who is investigating an important class of proteins that have been implicated in disease processes such as atherosclerosis and tumor growth. The program involves studying how the functions of these proteins are ultimately related to their unique structures as governed by weak interactions between various proteins and other molecules. The Professor Wei is characterizing these weak interactions in an effort to understand the similarities and differences of these protein functions and to provide new insights in enzymology. The project participants, including undergraduate and M.S. graduate students, acquire specialized training in protein preparation and characterization techniques, that enhance fundamental research programs at a primary undergraduate institution. The project also recruits underrepresented students and high school students to biochemical research. This research project uses biophysical techniques to elucidate the enzymatic mechanism of two related enzymes, NADPH oxidase 5 and dual oxidase. Their enzymatic activities are modulated by several factors including domain-domain and protein-protein interactions. These interactions are investigated by ultra-sensitive calorimetry and UV/fluorescence spectroscopy to obtain thermodynamic and kinetic parameters, as well as information about structural changes. In addition, the dissimilarities between their sequences, phosphorylation, and auxiliary protein recognition sites are investigated for their distinct activity profiles. Information from this study provides a molecular understanding of these two enzymes in regards to their catalysis and regulation, defining a new model system for exploring non-phagocyte NADPH Oxidases.

凭借该奖项，化学部的生命过程化学项目正在资助南伊利诺伊大学爱德华兹维尔分校的 Chin-Chuan Wei 博士，他正在研究一类与动脉粥样硬化和肿瘤生长等疾病过程有关的重要蛋白质。该计划涉及研究这些蛋白质的功能最终如何与其独特的结构相关，而这些独特的结构是由各种蛋白质和其他分子之间的弱相互作用控制的。魏教授正在表征这些弱相互作用，以期了解这些蛋白质功能的异同，并为酶学提供新的见解。项目参与者包括本科生和硕士。研究生获得蛋白质制备和表征技术方面的专门培训，以加强初级本科机构的基础研究项目。该项目还招募代表性不足的学生和高中生进行生化研究。该研究项目利用生物物理技术来阐明两种相关酶NADPH氧化酶5和双氧化酶的酶促机制。它们的酶活性受到多种因素的调节，包括结构域-结构域和蛋白质-蛋白质相互作用。通过超灵敏量热法和紫外/荧光光谱研究这些相互作用，以获得热力学和动力学参数以及有关结构变化的信息。此外，还研究了它们的序列、磷酸化和辅助蛋白质识别位点之间的差异，以了解它们不同的活性特征。这项研究的信息提供了对这两种酶的催化和调节的分子理解，定义了探索非吞噬细胞 NADPH 氧化酶的新模型系统。