Structure, mechanisms, regulation and assembly of ATP synthase

生物生命依赖于一种能源。这种能量来自阳光。它是通过绿色植物的光合作用获得的，并为我们所吃的食物提供高能量成分。我们通过燃烧(氧化)高能成分，以受控的方式释放细胞能量，以被称为三磷酸腺苷(或简称ATP)的分子的形式，在我们的体内收集能量，以产生生命的燃料。这一过程中的关键步骤发生在构成我们组织的细胞内的线粒体中。线粒体是由数百万个微小的分子涡轮机--三磷酸腺苷合成酶--组成的生物“发电站”，它们像人造涡轮机一样旋转，产生大量的细胞燃料，然后这些燃料被输送到我们身体的各个部位，提供能量使它们发挥作用。我们非常详细地了解了这些分子涡轮机如何工作的许多方面，但还不知道旋转作用是如何产生的。这个项目的一部分是关于提供关键的缺失信息。细菌有类似的涡轮机，在某些方面与人类的涡轮机不同。我们想更好地了解这些差异，这样我们就可以设计出药物来杀死病原体，比如导致结核病的细菌，方法是在不影响人类涡轮机的情况下停止它们的涡轮机。与人类涡轮机相关的，但不是ATP制造机制的一部分，是一个打开的通道，例如在心脏病发作期间，以一种不受控制的方式释放线粒体内容物，导致细胞死亡。我们想了解毛孔是如何工作的，这样我们就可以帮助设计其他药物来控制毛孔。

Biological life depends on a source of energy. That energy comes from sunlight. It is harvested by photosynthesis in green plants, and provides the high energy components in the foods that we eat. We harvest that energy in our bodies by "burning" (oxidising) the high energy components, releasing cellular energy in a controlled way to generate the fuel of life, in the form of the molecule known as adenosine triphosphate (or ATP for short). The key steps in this process take place in the mitochondria inside the cells that make up our tissues. The mitochondria are biological "power stations" full of millions of tiny molecular turbines, the ATP synthases, that rotate rather like man-made turbines churning out the cellular fuel in massive quantities, which is then delivered to all parts of our bodies to provide the energy to make them function. We understand in great detail many aspects of how these molecular turbines work, but as yet not how the rotary action is generated. Part of this project is about providing that crucial missing information. Bacteria have similar turbines that differ is some respects from the human turbines. We want to understand these differences better, so that we can devise drugs to kill pathogenic bacteria, such as the one that causes tuberculosis, by stopping their turbines without influencing the human ones. Associated with the human turbines, but not part of the ATP making machinery, is a channel that becomes opened, for example during a heart attack, letting out the contents of the mitochondria in an uncontrolled way leading to the death of the cell. We want to understand how this pore works, so that we can help design other drugs to control the pore.