PIONEERING RESEARCH ON THE DYNAMICAL ASPECT OF STRUCTURE-FUNTION RELATIONSHIP IN ION CHANNELS

近十年来，由于结合了分子生物学和膜钳技术，离子通道的结构和功能研究取得了很大进展。然而，分析离子通道结构-功能关系的动力学方面似乎仍然很困难，这主要是因为我们不知道如何测量通道分子的高阶结构的变化。本研究的目的是找出一条线索，如何检测和估计通道分子的高阶结构变化，并将它们与通道功能相关联。团队成员被分成三个小组，每个小组负责A)生物通道的结构-功能，B)模型通道的结构-功能，以及C)新显微技术的开发。后两个主题在本项目中尤为有特色和重要。我们可以合成世界上最简单的具有离子选择性或电压依赖性的结构通道分子，这将极大地帮助我们理解通道分子的动态结构-功能关联。此外，我们还发展了几种值得注意的显微技术：单个荧光分子的可视化，单通道运动的跟踪和操纵，笼状化合物和冷冻电子显微镜相结合的时间分辨精细结构分析。我们相信，这一成果将为详细分析离子通道结构-功能关联的动力学方面开辟一条新的途径。

Structuire-function studies of ion channels have greatly progressed in this decade owing to the conbination of molecular bilogical-and pacth clamp-techniques. However it seems still difficult to analyze the dynamical aspects of structure-function relationship in ion channels mainly because we do not know how to measure changes in the higher oder structure of channel molecules. The aim of the present research project was to find out a clue how to detect and estimate the higher order structural changes of channel molecules and to correlate them with channel functions. The team members have been divided into three sub-teams each of which conducted, A) structure-function of biological channels, B) structure-function of model channels, and C) development of new microscopy techniqes. The latter two subjects are particularly characteristic and important in this project. We could scceed to synthetize the world simplest structured channel molecules with ion selectivity or voltage dependecy, which may greatly help us to understand the dynamic structure-function correlation of channel molecules. In addition we have developed several remarkable microscopy techniques ; visualization of single fluorescent molecule, tracing and manipulation of of single channel motion, time-resolved fine structural analysis by the conbination of caged compounds and cryo-electron microscopy. We believe that this achievement would open up a way for the detailled analysis of dynamical aspects of structure-function correlation in ion channels.