Structure Mechanics and Regulation Of The Vacuolar ATPase.

液泡 ATP 酶的结构力学和调节。

• 批准号: G1000567/1
• 负责人: Stephen Muench
• 金额: $ 89.88万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000567%2F1
• 关键词: Structure; Mechanics; Regulation; Vacuolar; ATPase.

The vacuolar ATPase (V-ATPase) is a complex multi-component protein found in virtually all living cells. It is a miniature mechanical rotary motor, only thirty millionths of a millimetre long but capable of pushing protons into or out of specialised compartments in the cell, regulating acidity. The V-ATPase is a 3-stroke motor that uses ATP as a fuel to rotate a central axle, which is linked to a 10-stroke acid pump plugged into the cell membrane. A molecular gearbox links the two motors allowing it to push protons against different gradients. However, the way in which the motors work and are controlled by the cell are still unclear. This project aims to generate a high resolution structure, through electron microscopy and X-ray crystallography, revealing the composition and mechanism of this motor and its gearbox. Understanding the structure and mechanism of this motor will provide important information which can be used to develop new drugs, important because of the role the protein plays in a number of diseases including osteoporosis, kidney disease and cancer. By understanding the structure, mechanism and regulation of the protein we may be able to develop novel ways of switching it off with drugs in diseased tissue.

液泡atp酶（v - atp酶）是一种复杂的多组分蛋白，几乎存在于所有活细胞中。它是一种微型机械旋转马达，只有千分之三毫米长，但能够推动质子进出细胞内的专门隔间，调节酸度。v -ATP酶是一个3冲程的马达，它使用ATP作为燃料来旋转中心轴，中心轴与插入细胞膜的10冲程酸泵相连。一个分子齿轮箱将两个马达连接在一起，使它能够以不同的梯度推动质子。然而，马达的工作方式和细胞的控制方式仍然不清楚。本项目旨在生成高分辨率的结构，通过电子显微镜和x射线晶体学，揭示该电机及其齿轮箱的组成和机理。了解这种马达的结构和机制将为开发新药提供重要信息，因为这种蛋白质在包括骨质疏松症、肾病和癌症在内的许多疾病中发挥着重要作用。通过了解这种蛋白质的结构、机制和调控，我们或许能够开发出用药物在病变组织中关闭它的新方法。