Structure of a Complete ATP Synthase Dimer Reveals the Molecular Basis of Inner Mitochondrial Membrane Morphology.
Structure of a Complete ATP Synthase Dimer Reveals the Molecular Basis of Inner Mitochondrial Membrane Morphology.
复制标题
DOI：
10.1016/j.molcel.2016.05.037
复制
发表时间：
2016-08-04
期刊：
影响因子：
16
通讯作者：
Meier T
中科院分区：
文献类型：
--
作者：
Hahn A;Parey K;Bublitz M;Mills DJ;Zickermann V;Vonck J;Kühlbrandt W;Meier T
我们通过冷冻电镜和X射线晶体学的结合确定了来自酵母解脂耶氏酵母线粒体的完整二聚体F1 Fo-ATP合成酶的结构。最终的结构解析了60个二聚体亚基中的58个。Fo中亚基a的水平螺旋缠绕在c环转子周围，并且分配给亚基a、B、f、i和8的总共六个垂直螺旋跨越膜。亚基8（人类A6 L）是细菌B亚基的进化衍生物。在内腔膜表面，亚基f在两个单体之间建立直接接触。与冷冻电镜图的F1 Fo单体的比较，确定在侧二聚体界面的亚基e和g。它们不形成二聚体接触，但通过诱导100°的强膜曲率来形成二聚体。我们的结构解释了线粒体嵴形成的结构基础，这是真核细胞形态学的一个里程碑式的标志。酵母F1 Fo-ATP合酶二聚体的冷冻电镜结构F1头和转子复合体的无抑制剂X射线结构旋转催化产生ATP的机制线粒体内膜嵴形成的结构基础ATP酶是一种复杂的大分子机器，提供细胞中大部分的ATP。Hahn等人提出了一个完整的ATP合酶二聚体的结构，这提供了深入了解这些纳米马达的机制，以及它们如何导致膜弯曲形成嵴内线粒体膜。
We determined the structure of a complete, dimeric F1Fo-ATP synthase from yeast Yarrowia lipolytica mitochondria by a combination of cryo-EM and X-ray crystallography. The final structure resolves 58 of the 60 dimer subunits. Horizontal helices of subunit a in Fo wrap around the c-ring rotor, and a total of six vertical helices assigned to subunits a, b, f, i, and 8 span the membrane. Subunit 8 (A6L in human) is an evolutionary derivative of the bacterial b subunit. On the lumenal membrane surface, subunit f establishes direct contact between the two monomers. Comparison with a cryo-EM map of the F1Fo monomer identifies subunits e and g at the lateral dimer interface. They do not form dimer contacts but enable dimer formation by inducing a strong membrane curvature of ∼100°. Our structure explains the structural basis of cristae formation in mitochondria, a landmark signature of eukaryotic cell morphology. Cryo-EM structure of a yeast F1Fo-ATP synthase dimer Inhibitor-free X-ray structure of the F1 head and rotor complex Mechanism of ATP generation by rotary catalysis Structural basis of cristae formation in the inner mitochondrial membrane ATP synthases are complex macromolecular machines that supply most of the ATP in cells. Hahn et al. present the structure of a complete ATP synthase dimer, which provides insights into both the mechanism of these nanomotors and how they cause membrane bending to form cristae in the inner mitochondrial membrane.