Fish Electric Organ as a Factory for Membrane Proteins

项目摘要 结构生物学的一个目标是使蛋白质结构的确定像DNA一样常规 测序是现在。这一目标即将实现可溶性蛋白质， 主要由蛋白质晶体学家和NMR积累的丰富经验 光谱学家人类细胞膜实现这一目标的主要障碍是 目前可用的异源表达系统不能 常规地产生足够量的正确折叠的人膜蛋白， 原子级结构方法。人类的原子级结构的稀缺性 膜蛋白是一个问题，因为膜蛋白是常见的目标， 旨在改善人类健康的药物。这一提议的假设是， 产生大量内源性膜蛋白的真核细胞是良好的 作为新型异源蛋白表达系统基础的候选物 产生大量正确折叠的人类膜蛋白。这项建议 将用鱼类电器的电细胞来验证这一假设，这些电细胞是烟碱乙酰胆碱受体的异常高水平的生产者。

PROJECT SUMMARY 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.