STRUCTURE AND FUNCTION OF MECHANOSENSITIVE ION CHANNELS

机械敏感离子通道的结构和功能

• 批准号: 6651530
• 负责人: DENNIS A DOUGHERTY
• 金额: $ 90.66万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651530
• 关键词: membrane channels; peptide chemical synthesis; protein engineering; protein structure function

The Program Project Grant Structure and Function of Mechanosensitive Ion Channels brings together an array of technologies drawn from chemistry, biology, physics, and biotechnology to develop the most detailed structure/function analysis of an ion channel protein to date. Building on the foundation of the high resolution crystal structure of the Tb-MscL channel reported by Rees, the tools of structural biology, organic chemistry, determine how a channel responds to a stimulus and translates that stimulus into an observable signal. The four key components of the proposed program are: structure, function, synthesis, and redesign, and each of the parent MscL channel and on selected variants with the ultimate goal being a structure determination of the open state of the channel. High resolution electrophysiology techniques will correlate structure and function, and single molecule spectroscopy will provide unprecedented views of ion behavior. For the first time, total diversity involving both natural and unnatural modifications. A high throughput assay for MscL behavior will greatly aid the analysis of the structural variants prepared, and computer modeling will provide detailed insights into experimental observations. Since ion channels lie at the core of molecular neurobiology, the information obtained from this Project Grant will have far-reaching consequences. The list of neurological disorders associated with a malfunction in an ion channel protein is long and growing, and the information obtained here will be invaluable in understanding such disease states and in developing effective treatment strategies.

机械敏感离子通道的结构和功能计划项目资助汇集了一系列来自化学，生物学，物理学和生物技术的技术，以开发迄今为止最详细的离子通道蛋白质的结构/功能分析。在Rees报道的Tb-MscL通道的高分辨率晶体结构的基础上，结构生物学、有机化学的工具确定通道如何响应刺激并将该刺激转化为可观察的信号。所提出的计划的四个关键组成部分是：结构，功能，合成和重新设计，和每个父MscL通道和选定的变种，最终目标是一个结构确定的通道的开放状态。高分辨率的电生理学技术将使结构和功能相互关联，单分子光谱学将提供前所未有的离子行为视图。这是第一次，涉及自然和非自然修饰的总多样性。MscL行为的高通量测定将极大地帮助分析所制备的结构变体，并且计算机建模将为实验观察提供详细的见解。由于离子通道是分子神经生物学的核心，因此从这项计划补助金中获得的信息将产生深远的影响。与离子通道蛋白质功能障碍相关的神经系统疾病的列表很长，而且还在不断增长，这里获得的信息对于理解这种疾病状态和制定有效的治疗策略将是非常宝贵的。