Molecular Structure and Function Program, Hospital for Sick Children Research Institute, Toronto, ON, Canada M5G 1X8.
Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11675-80. doi: 10.1073/pnas.1204935109. Epub 2012 Jul 2.
Mitochondrial ATP synthase is responsible for the synthesis of ATP, a universal energy currency in cells. Whereas X-ray crystallography has revealed the structure of the soluble region of the complex and the membrane-intrinsic c-subunits, little is known about the structure of the six other proteins (a, b, f, A6L, e, and g) that comprise the membrane-bound region of the complex in animal mitochondria. Here, we present the structure of intact bovine mitochondrial ATP synthase at ∼18 Å resolution by electron cryomicroscopy of single particles in amorphous ice. The map reveals that the a-subunit and c(8)-ring of the complex interact with a small contact area and that the b-subunit spans the membrane without contacting the c(8)-ring. The e- and g-subunits extend from the a-subunit density distal to the c(8)-ring. The map was calculated from images of a preparation of the enzyme solubilized with the detergent dodecyl maltoside, which is visible in electron cryomicroscopy maps. The structure shows that the micelle surrounding the complex is curved. The observed bend in the micelle of the detergent-solubilized complex is consistent with previous electron tomography experiments and suggests that monomers of ATP synthase are sufficient to produce curvature in lipid bilayers.
线粒体 ATP 合酶负责合成 ATP，这是细胞中通用的能量货币。尽管 X 射线晶体学已经揭示了该复合物可溶性区域和膜内在 c 亚基的结构，但对于构成动物线粒体复合物膜结合区域的其他六种蛋白质（a、b、f、A6L、e 和 g）的结构知之甚少。在这里，我们通过在非晶冰中单颗粒的电子 cryo 显微镜术以约 18 Å 的分辨率呈现完整的牛线粒体 ATP 合酶的结构。该图谱显示，复合物的 a 亚基和 c（8）-环与小的接触区域相互作用，并且 b 亚基在不与 c（8）-环接触的情况下跨越膜。e 和 g 亚基从远离 c（8）-环的 a 亚基密度处延伸。该图谱是从用去污剂十二烷基麦芽糖溶解的酶制剂的图像中计算得出的，在电子 cryo 显微镜图谱中可以看到该去污剂。该结构表明，包围复合物的胶束是弯曲的。在去污剂溶解的复合物的胶束中观察到的弯曲与先前的电子断层扫描实验一致，表明 ATP 合酶的单体足以在脂质双层中产生曲率。
