Structure Mechanics and Regulation Of The Vacuolar ATPase.

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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.