Structure and function of the ATP synthase

线粒体F1Fo-ATP合成酶负责有氧条件下合成90%的ATP 条件。ATP合成酶是一种多聚体蛋白质复合体，其总分子量大于 550,000 Da.一部分三磷酸腺苷合成酶嵌入线粒体膜，起到质子的作用。 涡轮机和一部分位于基质空间中，充当使ADP磷酸化的旋转发动机。在前一次 在获奖期间，我们已经解决了F1-ATPase和 确定了F1突变的结构基础，该突变将质子转运从ATP合成中分离出来。这个 三磷酸腺苷合成酶的偶联是能量代谢的关键，但其机制却知之甚少。我们 还测定了酵母菌C10环的高分辨结构，在pH 5.5，6.1，8.3，经 Dcd，并与寡霉素结合。目前的项目建立在我们的进步之上，并扩大了我们的目标。 该项目的一个目标是确定ATP合成酶复合体的高分辨率晶体结构 酿酒酵母。这一目标将给出关键的结构细节，以了解 与三磷酸腺苷合成相关的质子转运。一些基因修改将被用来促进 整个复合体的结晶。ATP合成酶的高分辨率结构将提供关键的 了解和治疗癌症和糖尿病等疾病的功能。

The mitochondrial F1Fo ATP synthase is responsible for the synthesis 90% of the ATP under aerobic conditions. The ATP synthase is a multimeric protein complex with an overall molecular weight greater than 550,000 Da. A portion of the ATP synthase is embedded in the mitochondrial membrane and acts as a proton turbine and a portion is in the matrix space and acts as a rotary engine that phosphorylates ADP. In the prior award period, we have solved the high resolution structures of 4 mutant forms of the F1 ATPase and determined the structural basis of mutations in F1 that uncouple proton translocation from ATP synthesis. The coupling of the ATP synthase is key to energy metabolism and yet the mechanism is poorly understood. We have also determined the high-resolution structures of the yeast c10-ring at pH 5.5, 6.1, 8.3, modified with DCCD, and bound with oligomycin. The current project builds upon our advances and expands our goals. One aim of this project is to determine the high-resolution crystal structure of the ATP synthase complex from yeast S. cerevisiae. This aim will give critical structural details into the understanding of the mechanism of proton translocation coupled to ATP synthesis. A number of genetic modifications will be used to facilitate crystallization of the entire complex. The high-resolution structure of the ATP synthase will provide the critical features to understand and treat diseases such as cancer and diabetes.