Developing Oriented Circular Dichroism Spectroscopy as a Methodological Tool for Characterising Membrane Proteins

膜蛋白是一种在细胞周围磷脂双层中具有重要生理意义的分子。它们是大量药物的目标，因为它们中的许多在发生突变时是疾病的原因。大多数检测膜蛋白的方法都要求将蛋白质周围的膜用洗涤剂溶解，这就消除了它们之间以及与周围脂质之间的相互作用，而这些相互作用可能对它们的功能很重要。本建议是开发一种方法学工具，使我们能够检查完整膜中的蛋白质，从而保留其天然结构。这种方法，定向圆二色光谱，将能够检查它们的局部结构和与它们如何工作相关的结构和方向的变化。

Membrane proteins are physiologically-important molecules that are embedded in the phospholipid bilayers surrounding cells. They are the targets of a large number of pharmaceutical drugs because many of them, when mutated, are the causes of diseases. Most methods for examining membrane proteins require that the membranes that surround the proteins be dissolved by detergents, which removes interactions both with each other and with the surrounding lipids that may be important to their functioning. This proposal is to develop a methodological tool that will enable us to examine proteins in intact membranes, thereby preserving their native structure. The method, Oriented Circular Dichroism spectroscopy, would enable the examination of both their local structure and the changes in their structure and orientation associated with how they work.