Fish Electric Organ as a Factory for Membrane Proteins

鱼电器官作为膜蛋白的工厂

• 批准号: 7910390
• 负责人: Rene Anand
• 金额: $ 30.6万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-10 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7910390
• 关键词: Cells; DNA Sequence; Disease; Drug Design; Electric Organ; Eukaryotic Cell; Foundations; Goals; Health; Heart Diseases; Human; Knowledge; Membrane; Membrane Proteins; Mental disorders; Methodology; Neurodegenerative Disorders; Nicotinic Receptors; Normal Cell; Proteins; Public Health; Shapes; Structure; System; Testing; Work; experience; improved; novel; protein expression; protein structure; public health relevance; structural biology

DESCRIPTION (provided by applicant): A goal of structural biology is to make protein structure determination as routine as DNA sequencing is now. That goal is coming within reach for soluble proteins through extensive experience accumulated primarily by protein crystallographers and NMR spectroscopists. The major obstacle to progress toward that goal for human membrane proteins is the inability of currently available heterologous expression systems to routinely produce sufficient amounts of correctly folded, human membrane proteins for atomic level structure methodologies. The scarcity of atomic level structures of human membrane proteins is a problem because membrane proteins are frequent targets for drugs designed to improve human health. The hypothesis for this proposal is that eukaryotic cells producing large amounts of endogenous membrane proteins are good candidates as the foundation for novel heterologous protein expression systems producing large amounts of correctly folded human membrane proteins. This proposal will test this hypothesis with electrocytes from fish electric organ, which are exceptionally high level producers of nicotinic acetylcholine receptors. PUBLIC HEALTH RELEVANCE: The scarcity of atomic level knowledge about the shapes of human membrane proteins is a problem because membrane proteins are crucial to human health and to many diseases. Membrane proteins allow cells to communicate with the external world and between membrane-divided compartments within a cell. Knowing the shapes of membrane proteins is important not only for understanding how normal cells work. This understanding also helps develop disease therapies and preventions, for example, by guiding drug design. Diseases involving membrane proteins are major public health problems including neurodegenerative diseases, mental illnesses, and heart disease.

描述（由申请人提供）：结构生物学的目标是使蛋白质结构确定为常规，就像DNA测序一样。通过主要由蛋白质晶体学家和NMR光谱学家积累的丰富经验，可溶性蛋白质的目标是实现的目标。朝着人类膜蛋白进行该目标的主要障碍是目前可用的异源表达系统常规生产足够数量的正确折叠的人膜蛋白来用于原子水平结构方法。人膜​​蛋白的原子水平结构的稀缺是一个问题，因为膜蛋白是旨在改善人类健康的药物的常见靶标。该建议的假设是，产生大量内源性膜蛋白的真核细胞是良好的候选物，是新型异源蛋白表达系统的基础，产生了大量正确折叠的人膜蛋白。该提案将用Fish Electry Organ的电细胞检验该假设，FISH电机是烟碱乙酰胆碱受体的高水平生产者。公共卫生相关性：关于人膜蛋白质形状的原子水平知识的稀缺性是一个问题，因为膜蛋白对人类健康和许多疾病至关重要。膜蛋白允许细胞与外部世界以及细胞内的膜划分区隔间进行通信。了解膜蛋白的形状不仅对于理解正常细胞的工作方式而言至关重要。这种理解还有助于通过指导药物设计来开发疾病疗法和预防。涉及膜蛋白的疾病是主要的公共卫生问题，包括神经退行性疾病，精神疾病和心脏病。