Understanding trafficking and membrane localization to re-engineer host and GPCR protein for improved expression

了解运输和膜定位以重新设计宿主和 GPCR 蛋白以改善表达

• 批准号: 1249200
• 负责人: Anne Robinson
• 金额: $ 18.07万
• 依托单位: Tulane University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1249200&HistoricalAwards=false
• 关键词: Understanding; trafficking; membrane; localization; re

This NSF award by the Biotechnology, Biochemical and Biomass Engineering program supports work to develop improved expression systems for integral membrane proteins. Integral membrane proteins play critical roles in cell signaling, and are implicated in a wide range of human diseases such as asthma, obesity, cancer, heart disease, and chronic pain. Biophysical and biochemical studies of membrane proteins require large quantities of purified protein; even more than soluble proteins, because they need to be solubilized in detergent solutions. Results for many classes of membrane proteins suggest that in traditional expression systems, valuable targets of drug discovery and biochemical importance will be understudied because researchers cannot make sufficient protein. The goal of this research effort is to improve the expression of an important class of membrane proteins, the G protein-coupled receptor family (GPCRs). Specific aims are to identify cellular and molecular features of both the proteins and expression host to achieve the highest level of active GPCRs for structural and biophysical characterization. In addition, specific educational examples will be developed for the undergraduate Heat and Mass Transfer course. Graduate and undergraduate students will be trained in the laboratory, with particular efforts focused on representation from women and under-represented groups.

这项由生物技术，生物化学和生物质工程计划授予的NSF奖项支持开发改进的完整膜蛋白表达系统的工作。 整合膜蛋白在细胞信号传导中起关键作用，并且与广泛的人类疾病如哮喘、肥胖、癌症、心脏病和慢性疼痛有关。膜蛋白的生物物理和生化研究需要大量纯化的蛋白质;甚至比可溶性蛋白质还要多，因为它们需要溶解在洗涤剂溶液中。许多类型的膜蛋白的结果表明，在传统的表达系统中，药物发现和生物化学重要性的有价值的目标将被研究不足，因为研究人员不能使足够的蛋白质。这项研究工作的目标是提高一类重要的膜蛋白，G蛋白偶联受体家族（GPCR）的表达。具体目标是鉴定蛋白质和表达宿主的细胞和分子特征，以获得最高水平的活性GPCR，用于结构和生物物理表征。此外，具体的教育实例将开发为本科生热与质量传递课程。研究生和本科生将在实验室接受培训，特别注重妇女和代表性不足群体的代表性。