Structure Mechanics and Regulation Of The Vacuolar ATPase.

液泡ATP酶（V-ATP酶）是一种复杂的多组分蛋白质，几乎存在于所有活细胞中。它是一个微型的机械旋转马达，只有三百万分之一毫米长，但能够推动质子进出细胞中的专门区域，调节酸度。V-ATP酶是一种三冲程发动机，它使用ATP作为燃料来旋转中心轴，该中心轴与插入细胞膜的10冲程酸泵相连。一个分子齿轮箱连接着两个马达，使其能够推动质子对抗不同的梯度。然而，马达的工作方式以及由细胞控制的方式仍然不清楚。该项目旨在通过电子显微镜和X射线晶体学生成高分辨率结构，揭示该电机及其齿轮箱的组成和机制。了解这种马达的结构和机制将提供可用于开发新药的重要信息，因为蛋白质在许多疾病中发挥作用，包括骨质疏松症，肾脏疾病和癌症。通过了解这种蛋白质的结构、机制和调控，我们可能能够开发出新的方法，在患病组织中用药物关闭它。

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.