MECHANISM OF ION TRANSPORT THROUGH MEMBRANE CHANNELS

拟议的研究旨在详细了解 生物膜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是重要的， 细胞或组织与其环境或其他部分的沟通 多成分有机体 该项目采用“自下而上”的方法， 离子通道的设计和作用机制， 化学定义的“基线”系统，然后引入一系列 微妙的化学变化，其中一些将显着影响 重要的通道特性，如离子选择性、电压 依赖性和膜中通道的组装。 对于这些类型 短杆菌肽家族的膜通道提供了几个 优点：（i）已知的三级结构;（ii）定义明确且 特征通道功能;（iii）对氨基酸的顺应性 序列取代和其他化学修饰;和（iv） 生物物理学方法的适用性， 表征的结构和功能特性， 与父信道相关的修改信道。 拟议 短杆菌肽家族通道的研究旨在进一步 理解支配结构-功能的一般原则 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.