Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY Cambridge, United Kingdom.
Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, CB2 0XY Cambridge, United Kingdom
Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29602-29608. doi: 10.1073/pnas.2017987117. Epub 2020 Nov 9.
The adenosine triphosphate (ATP) synthase in human mitochondria is a membrane bound assembly of 29 proteins of 18 kinds organized into F-catalytic, peripheral stalk (PS), and c-rotor ring modules. All but two membrane components are encoded in nuclear genes, synthesized on cytoplasmic ribosomes, imported into the mitochondrial matrix, and assembled into the complex with the mitochondrial gene products ATP6 and ATP8. Intermediate vestigial ATPase complexes formed by disruption of nuclear genes for individual subunits provide a description of how the various domains are introduced into the enzyme. From this approach, it is evident that three alternative pathways operate to introduce the PS module (including associated membrane subunits e, f, and g). In one pathway, the PS is built up by addition to the core subunit b of membrane subunits e and g together, followed by membrane subunit f. Then this b-e-g-f complex is bound to the preformed F-c module by subunits OSCP and F The final component of the PS, subunit d, is added subsequently to form a key intermediate that accepts the two mitochondrially encoded subunits. In another route to this key intermediate, first e and g together and then f are added to a preformed F-c-OSCP-F-b-d complex. A third route involves the addition of the c-ring module to the complete F-PS complex. The key intermediate then accepts the two mitochondrially encoded subunits, stabilized by the addition of subunit j, leading to an ATP synthase complex that is coupled to the proton motive force and capable of making ATP.
人线粒体中的三磷酸腺苷（ATP）合酶是由 29 种蛋白质组成的膜结合体，分为 F 催化、外周柄（PS）和 c-转子环模块。除了两个膜成分外，所有其他成分都是由核基因编码的，在细胞质核糖体上合成，然后导入线粒体基质中，并与线粒体基因产物 ATP6 和 ATP8 组装在一起。由于核基因中断导致形成的中间残余 ATP 酶复合物，提供了对各个亚基的不同结构域如何被引入酶中的描述。从这种方法可以明显看出，有三种替代途径可以引入 PS 模块（包括相关的膜亚基 e、f 和 g）。在一种途径中，PS 通过将膜亚基 e 和 g 一起添加到核心亚基 b 上构建，然后添加膜亚基 f。然后，这个 b-e-g-f 复合物通过 OSCP 和 F 亚基与预先形成的 F-c 模块结合。PS 的最后一个组件亚基 d 随后被添加以形成接受两个线粒体编码亚基的关键中间体。在另一条通向这个关键中间体的途径中，首先是 e 和 g 一起，然后是 f，添加到预先形成的 F-c-OSCP-F-b-d 复合物中。第三种途径涉及将 c 环模块添加到完整的 F-PS 复合物中。然后，关键中间体接受两个线粒体编码的亚基，通过添加亚基 j 来稳定，导致与质子动力势耦合并能够产生 ATP 的 ATP 合酶复合物。
