Mechanism of protein denaturation by SDS

SDS 使蛋白质变性的机制

• 批准号: 386528-2010
• 负责人: Privé, Gilbert
• 金额: $ 2.19万
• 依托单位: University of Toronto
• 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=507135
• 关键词: Mechanism; protein; denaturation; SDS

This research combines two areas of study - protein/detergent interactions and protein folding. Certain kinds of detergents called ionic detergents are very effective at binding to proteins. This strong binding changes the shape of the protein, and because proteins are normally tightly folded up into precise 3D shapes, these strongly binding detergents unfold the protein. This usually destroys the function of the protein, but the detergent-unfolded state can be used in many protein biotechnology applications. For example, one of the most widely used analytical methods in biochemistry labs is to measure the molecular weight of detergent-unfolded proteins by electrophoresis. Despite the common use of detergents in these applications, we do not know how ionic detergents bind to proteins. One of the goals of this research is to understand how and why these detergents bind so strongly to proteins. On a second front, my lab has discovered a simple way to change the protein binding properties of ionic detergents. With this method, we can convert a strongly binding detergent into a weakly binding detergent. The weakly binding form of the detergent does not unfold protein, and this method has potential applications in the production of folded protein that cannot be obtained by other methods. Our investigations into the fundamental mechanism of detergent binding to proteins may lead to improved methods for producing protein in the biotechnology and the pharmaceutical industries.

这项研究结合了两个研究领域-蛋白质/洗涤剂相互作用和蛋白质折叠。某些被称为离子洗涤剂的洗涤剂在与蛋白质结合方面非常有效。这种强结合改变了蛋白质的形状，因为蛋白质通常紧密地折叠成精确的3D形状，这些强结合的洗涤剂会将蛋白质展开。这通常会破坏蛋白质的功能，但洗涤剂-展开状态可用于许多蛋白质生物技术应用。例如，生物化学实验室中使用最广泛的分析方法之一是通过电泳测量洗涤剂未折叠蛋白的分子量。尽管在这些应用中通常使用洗涤剂，但我们不知道离子洗涤剂如何与蛋白质结合。这项研究的目标之一是了解这些洗涤剂如何以及为什么与蛋白质如此紧密地结合。在另一方面，我的实验室发现了一种简单的方法来改变离子洗涤剂的蛋白质结合特性。用这种方法，我们可以将强结合的洗涤剂转化为弱结合的洗涤剂。洗涤剂的弱结合形式不会展开蛋白质，该方法在生产其他方法无法获得的折叠蛋白质方面具有潜在的应用。我们对洗涤剂与蛋白质结合的基本机制的研究可能会改善生物技术和制药工业中生产蛋白质的方法。