Fish Electric Organ as a Factory for Membrane Proteins

鱼电器官作为膜蛋白的工厂

基本信息

批准号：
8310108
负责人：
Rene Anand
金额：
$ 30.34万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-10 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8310108
关键词：
Amino Acid Sequence Amino Acids Bacteria Bacterial Proteins Biochemical Cells Cholinergic Receptors Crystallization Crystallography DNA Sequence Detergents Disease Drug Design Electric Eel Electric Organ Electron Nuclear Double Resonance Electron Spin Resonance Spectroscopy Eukaryotic Cell Fluorescence Foundations Future Goals Halobacterium salinarium Health Heart Diseases Human Individual Insecta Ion Channel Joints Knowledge Label Membrane Membrane Proteins Mental disorders Methodology Methods Mutagenesis Mutate Mutation NMR Spectroscopy National Institute of General Medical Sciences Nervous system structure Neurodegenerative Disorders Neuromuscular Junction New York Nicotinic Receptors Normal Cell Peptide Sequence Determination Physiological Prevention therapy Procedures Production Property Protein Structure Initiative Proteins Public Health Resolution Resources Rhodopsin Shapes Solubility Solutions Source Structure System Technology Testing Torpedo United States National Institutes of Health Work X-Ray Crystallography Yeasts analytical ultracentrifugation design experience improved infrared spectroscopy light scattering meetings milligram novel protein expression protein folding protein structure solid state solid state nuclear magnetic resonance structural biology structural genomics technology development tool voltage

项目摘要

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.

项目摘要结构生物学的目的是使蛋白质结构确定为常规的DNA 现在是测序。这个目标是通过主要由蛋白质晶体学家和NMR积累的丰富经验光谱学家。朝着人类膜目标迈进的主要障碍蛋白质是当前可用的异源表达系统通常会产生足够数量的正确折叠的人膜蛋白原子级结构方法。人类原子水平结构的稀缺膜蛋白是一个问题，因为膜蛋白是常见的目标旨在改善人类健康的药物。该提议的假设是产生大量内源性膜蛋白的真核细胞很好候选人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。这个建议将用Fish电器官的电细胞检验该假设，这是烟碱乙酰胆碱受体的异常高水平的生产者。