Electrophoretic Measurements of Protein Folding Intermediates

蛋白质折叠中间体的电泳测量

• 批准号: 0317032
• 负责人: Jason Shear
• 金额: --
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0317032&HistoricalAwards=false
• 关键词: Electrophoretic; Measurements; Protein; Folding; Intermediates

Professor Jason Shear of the University of Texas Austin will work with Professors Eric Anslyn and Andrew Ellington on a project in bioanalytical chemistry supported by the Analytical and Surface Chemistry Program. The PI initiated a gated ultra-fast electrophoretic separations method in his previous award in the CAREER program. The idea is to cage a molecule, activate it photochemically, do a separation in microseconds and then detect the compounds using light in a time-of-flight analogy. This project centers on the application of that method to the problem of protein folding. Novel photochemical triggering with the help of site-directed mutagenesis to achieve the desired chemistry are being explored. Two model proteins will be used: cytochrome c and apomyoglobin. The project combines analytical and physical chemistry, organic synthesis and molecular biology to develop and evaluate a novel instrument for fast and sensitive detection of protein folding processes. The research is motivated by the question of how protein sequence specifies conformation, a major unanswered question in biology. There is thus a great need for quantitative information about the energetics and dynamics of protein refolding. The role of misfolded proteins is implicated but not well understood in a growing number of diseases such as Alzheimer's disease.

德克萨斯大学奥斯汀大学的Jason Shear教授将与Eric Anslyn和Andrew Ellington教授合作，由分析和表面化学计划支持的生物分析化学项目。 PI在他以前的职业计划中启动了封闭的超快速电泳分离方法。 这个想法是要笼子一个分子，在光化学上激活IT，在微秒内进行分离，然后在飞行时间类比中使用光检测化合物。 该项目以该方法在蛋白质折叠问题上的应用为中心。 正在探索新型的光化学触发，借助定点诱变以实现所需的化学。 将使用两种模型蛋白：细胞色素C和阿霉素。 该项目结合了分析和物理化学，有机合成和分子生物学，以开发和评估一种新颖的仪器，以快速和敏感的蛋白质折叠过程。 这项研究是由蛋白质序列如何指定构象的问题的动机，这是生物学中的主要未解决问题。因此，需要有关蛋白质重折叠的能量和动力学的定量信息。 在越来越多的阿尔茨海默氏病等疾病中，错误折叠蛋白的作用涉及但尚未得到充分理解。