MECHANISM OF ION TRANSPORT THROUGH MEMBRANE CHANNELS

拟议的研究旨在详细了解 生物膜中离子通道的结构和功能 分子水平，以及这些通道在细胞通讯中的作用。 离子通道对于信号的传输很重要，它允许 细胞或组织与其环境或与其其他部分进行交流 一个多组分的有机体。这个项目采用“自下而上”的方法 离子通道的设计和作用机理，从一种 化学定义的“基线”系统，然后引入了一系列 微妙的化学变化，其中一些将显著影响 重要的通道属性，如离子选择性、电压 依赖性，以及膜中通道的组装。对于这些类型 在实验中，膜通道蛋白家族提供了几种 优势：(一)已知的三级结构；(二)定义明确、结构良好 以通道功能为特征的；(Iii)对氨基酸的适应性 序列替换和其他化学修饰；和(Iv)一个 对生物物理方法的适应性，这些方法已经为 表征了其结构和功能特性 与父频道相关的已修改频道。建议数 对Granicidin通道家族的研究旨在进一步 对支配结构-功能的一般原则的理解 离子选择性膜通道的关系。

The proposed research is directed toward a detailed understanding of the structure and function of ion channels in biological membranes at the molecular level, and of the role of such channels in cell communication. Ion channels are important for the transmission of signals that allow a cell or tissue to communicate with its environment or with other parts of a multicomponent organism. This project takes a "bottom-up" approach to the design and mechanism of action of ion channels, starting with a chemically defined "baseline" system and then introducing a series of subtle chemical changes, some of which will significantly influence important channel properties, such as the ion selectivity, the voltage dependence, and the assembly of channels in membranes. For these types of experiments, the gramicidin family of membrane channels offers several advantages: (i) a known tertiary structure; (ii) a well defined and well characterized channel function; (iii) an amenability to amino acid sequence substitutions and other chemical modifications; and (iv) an amenability to biophysical methods that have been well established for characterizing both the structures and the functional properties of modified channels in relation to the parent channels. The proposed investigations of the gramicidin family of channels are aimed at further understanding of general principles that govern structure-function relationships for ion-selective membrane channels.