OPEN STATE STRUCTURE OF THE GATED MECHANOSENSOR MSCL

门控机械传感器 MSCL 的开态结构

• 批准号: 6209539
• 负责人: RANDAL B BASS
• 金额: $ 3.24万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6209539
• 关键词: X ray crystallography; conformation; crystallization; mechanoreceptors; membrane channels; potassium channel; protein structure function

The goal of the proposed research is to characterize an open (conducting) form of the mechanosensitve channel MscL. We will employ a several approaches including site-directed spin labeling, disulfide scanning and X-ray crystallography to elucidate the open state structure and mechanism of activation of this ion channel. Mechanosensitive channels have been found in all basic branches of the phylogenetic tree, and have been observerved in multiple tissue types in humans. A large percentage of current pharmaceuticals are targeted to ion channels, yet the mechanism of how these channels are opened and closed (gated) remains unknown. The recent structural determination of the mechanosensitive channel MscL in a closed conformation provided the first high resolution picture of this ubiquitous class of protein. The MscL protein is currently the only available system with which to study, at a high level of structural resolution, how ion channels are gated. To aid in crystallization, site-directed spin labeling and disulfide scanning studies will also be performed to both provide materail suitable for crystallization, i.e. in an open state, as well as determine more general information on channel gating.

本研究的目标是表征机械敏感通道 MscL 的开放（传导）形式。 我们将采用多种方法，包括定点自旋标记、二硫键扫描和X射线晶体学来阐明该离子通道的开放态结构和激活机制。 在系统发育树的所有基本分支中都发现了机械敏感通道，并且在人类的多种组织类型中都观察到了机械敏感通道。 目前大部分药物都是针对离子通道的，但这些通道如何打开和关闭（门控）的机制仍然未知。 最近对闭合构象中的机械敏感通道 MscL 的结构测定提供了此类普遍存在的蛋白质的第一张高分辨率图片。 MscL 蛋白是目前唯一可用的系统，可用于以高水平的结构分辨率研究离子通道的门控方式。 为了帮助结晶，还将进行定点自旋标记和二硫键扫描研究，以提供适合结晶（即处于开放状态）的材料，并确定有关通道选通的更一般信息。