Fish Electric Organ as a Factory for Membrane Proteins

项目总结 结构生物学的一个目标是使蛋白质结构测定像DNA一样成为常规 测序现在开始了。这一目标对可溶性蛋白质来说是触手可及的 主要由蛋白质结晶学家和核磁共振积累的丰富经验 光谱学家。人类膜实现这一目标的主要障碍是 蛋白质是目前可用的异源表达系统无法 常规生产足够数量的正确折叠的人膜蛋白 原子级结构方法论。人类原子级结构的稀缺性 膜蛋白是一个问题，因为膜蛋白经常是 旨在改善人类健康的药物。这项提议的假设是 真核细胞产生大量内源性膜蛋白是好的 候选蛋白作为新型异源蛋白表达系统的基础 产生大量正确折叠的人膜蛋白。这项建议 将用来自鱼类电子器官的细胞来验证这一假设，这些细胞是烟碱型乙酰胆碱受体的异常高水平的产生者。

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.