Structural basis for TOR activation by the HSP90-R2TP-TTT molecular chaperone complex

点击翻译按钮获取中文摘要

The normal and healthy functioning of cells is controlled by a plethora of nano-molecuiar machines which are made up of protein molecules, each of whose shape and mechanism of action is defined by the genetic information encoded in DNA. Assembly of many of these nano-machines, requires help from specialised nano-machines called chaperones, which look after component proteins until they are required, and ensure that the correct components are combined into the final working nano-machine.One of the most important of these chaperones is called HSP90. This is responsible for assisting the assembly of many of the nano-machines that monitor the health of the cell and transmit messages between and within cells. One of these - TOR - is particularly important for monitoring the nutritional health of the cell, and over-activity or defects in TOR are associated with diseases such as cancer, diabetes and unhealthy ageing.We wish to understand how the HSP90 chaperone, with the collaboration of two other nano-machines R2TP and TTT, facilitates the assembly of nano-machines based around TOR. To do this we will use very high magnification electron microscopes and intense X-ray beams, to look at the atomic structures of the different nano-machines involved, to work out which parts are critical for activity, and which parts of different nano-machines make contact with each other during the assembly process. This information will help us understand how TOR is regulated by these chaperones, and will point at new ways of controlling TOR activity with novel drugs.