Horizontal membrane-intrinsic α-helices in the stator a-subunit of an F-type ATP synthase
Horizontal membrane-intrinsic α-helices in the stator a-subunit of an F-type ATP synthase
复制标题
DOI：
10.1038/nature14185
复制
发表时间：
2015-05-14
期刊：
影响因子：
64.8
通讯作者：
Davies, Karen M.
中科院分区：
文献类型：
--
作者：
Allegretti, Matteo;Klusch, Niklas;Davies, Karen M.
ATP是细胞的通用能量货币，由F型ATP酶产生，这是一种古老的膜结合纳米机器。F型ATP酶利用跨膜电化学梯度的能量通过旋转催化产生ATP。穿过膜的质子驱动由8-15个c亚基组成的转子环（1）。中心柄将c环的旋转传递到催化F-1头部，在那里一系列构象变化导致ATP合成（2）。在这个基本过程中，一个关键的未解决的问题是质子如何通过膜来驱动ATP的产生。线粒体ATP酶在嵴膜中形成V形同源二聚体（3）。在这里，我们报告的结构，一个本地和活性线粒体ATP合酶二聚体，由单粒子电子低温显微镜在6.2埃分辨率。我们的结构显示了四个长的，水平的膜内α-螺旋的a-亚基，安排在两个发夹在一个角度约70度的c-环螺旋。有人提出，a亚基中严格保守的膜嵌入精氨酸将质子移位与c环旋转偶联（4）。保守的羧基末端a亚基序列的匹配将保守的精氨酸放置在质子结合c亚基谷氨酸的旁边。该图显示了从线粒体基质延伸到保守精氨酸的倾斜溶剂可接近通道。内腔膜表面的另一个亲水性空腔定义了质子到必需的组氨酸-谷氨酸对的直接路径（5）。我们的研究结果提供了独特的新的见解旋转ATP酶的结构和功能，并解释如何ATP生产耦合到质子易位。
ATP, the universal energy currency of cells, is produced by F-type ATP synthases, which are ancient, membrane-bound nanomachines. F-type ATP synthases use the energy of a transmembrane electrochemical gradient to generate ATP by rotary catalysis. Protons moving across the membrane drive a rotor ring composed of 8-15 c-subunits(1). A central stalk transmits the rotation of the c-ring to the catalytic F-1 head, where a series of conformational changes results in ATP synthesis(2). A key unresolved question in this fundamental process is how protons pass through the membrane to drive ATP production. Mitochondrial ATP synthases form V-shaped homodimers in cristae membranes(3). Here we report the structure of a native and active mitochondrial ATP synthase dimer, determined by single-particle electron cryomicroscopy at 6.2 angstrom resolution. Our structure shows four long, horizontal membrane-intrinsic alpha-helices in the a-subunit, arranged in two hairpins at an angle of approximately 70 degrees relative to the c-ring helices. It has been proposed that a strictly conserved membrane-embedded arginine in the a-subunit couples proton translocation to c-ring rotation(4). A fit of the conserved carboxy-terminal a-subunit sequence places the conserved arginine next to a proton-binding c-subunit glutamate. The map shows a slanting solvent-accessible channel that extends from the mitochondrial matrix to the conserved arginine. Another hydrophilic cavity on the lumenal membrane surface defines a direct route for the protons to an essential histidine-glutamate pair(5). Our results provide unique new insights into the structure and function of rotary ATP synthases and explain how ATP production is coupled to proton translocation.