Structure and function of the ATP synthase

线粒体F1 Fo ATP合成酶负责有氧条件下90%的ATP合成 条件ATP合酶是一种多聚体蛋白复合物，其总分子量大于 ATP合酶的一部分嵌入线粒体膜中并作为质子 涡轮机和一部分在基质空间中并用作磷酸化ADP的旋转发动机。现有 在获奖期间，我们已经解决了F1 ATP酶的4种突变形式的高分辨率结构， 确定了F1突变的结构基础，这些突变使质子转运与ATP合成分离。的 ATP合酶的偶联是能量代谢的关键，但其机制尚不清楚。我们 还确定了酵母c10-环在pH 5.5，6.1，8.3的高分辨率结构，用 DCCD，并与寡霉素结合。目前的项目建立在我们的进步和扩大我们的目标。 该项目的一个目的是确定ATP合酶复合物的高分辨率晶体结构， 酵母酿酒啤酒。这一目标将提供关键的结构细节的机制的理解， 质子转运与ATP合成偶联。一些基因改造将用于促进 整个复合体的结晶。ATP合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.