Dynamics and folding of a membrane protein and transcription activator

膜蛋白和转录激活剂的动力学和折叠

• 批准号: 41618-2011
• 负责人: ONeil, Joe
• 金额: $ 2.91万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=506152
• 关键词: Dynamics; folding; membrane; protein; transcription

A lipid membrane surrounds all animal, plant, and bacterial cells. Protein channels and receptors embedded in the lipid precisely control the flow of nutrients, waste products, energy, and information into and out of cells, but are poorly understood. Our long-term goal is to develop methods to overcome the many difficulties in membrane protein structure, folding and dynamics analysis. Recently, we have made progress in studying the folding of a bacterial membrane protein, the glycerol facilitator in detergent environments. We propose to continue this work by applying a new method for synthesizing the protein using cellular extracts and studying folding of the protein in a lipid membrane environment. Cell-free synthesis opens up the possibility of labelling the protein with isotopes for analysis by Nuclear Magnetic Resonance (NMR) spectroscopy, a method analogous to Magnetic Resonance Imaging (MRI). With labeled protein, we will study the detailed atomic dynamics of the protein that are key to understanding its biological transport mechanism. We will also continue our work along similar lines on the fungal antibiotic peptide alamethicin that is a model membrane protein.

脂质膜包围所有动物、植物和细菌细胞。嵌入脂质中的蛋白质通道和受体精确控制营养物质、废物、能量和信息进出细胞的流动，但人们对此知之甚少。我们的长期目标是开发方法来克服膜蛋白结构、折叠和动力学分析中的许多困难。最近，我们在研究细菌膜蛋白（洗涤剂环境中的甘油促进剂）的折叠方面取得了进展。我们建议通过应用一种使用细胞提取物合成蛋白质的新方法并研究蛋白质在脂膜环境中的折叠来继续这项工作。 无细胞合成开辟了用同位素标记蛋白质以通过核磁共振 (NMR) 光谱进行分析的可能性，这是一种类似于磁共振成像 (MRI) 的方法。 通过标记的蛋白质，我们将研究蛋白质的详细原子动力学，这是理解其生物转运机制的关键。我们还将继续沿着类似的思路研究真菌抗生素肽阿拉甲辛（一种模型膜蛋白）。