Assembly of the membrane domain of ATP synthase in human mitochondria
Assembly of the membrane domain of ATP synthase in human mitochondria
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DOI：
10.1073/pnas.1722086115
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发表时间：
2018-03-20
影响因子：
11.1
通讯作者：
Walker, John E.
中科院分区：
文献类型：
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作者：
He, Jiuya;Ford, Holly C.;Walker, John E.
人线粒体ATP合酶是由18种29种蛋白组成的膜结合体。除了两种膜成分外，所有膜成分都在核基因中编码，在细胞质核糖体上合成，然后进入细胞器基质，在那里它们与线粒体DNA中重叠基因的产物ATP6和ATP8组装成复合物。酶的膜部分核编码亚基的单个人类基因的破坏导致中间退化atp酶复合物的形成，该复合物提供了膜结构域组装途径的描述。关键的中间复合物由atp酶抑制剂蛋白IF1抑制的f -1-c8复合物组成，附着于外周茎，亚基e、f和g与外周茎的膜结构域相关。该中间体为在线粒体核糖体上合成的ATP6和ATP8的插入提供模板。它们与配合物的结合通过添加6.8蛋白脂来稳定，并且该配合物在此时与ATP合成偶联。二聚体酵母F-o膜结构域的结构与这种组装模型一致。人类6.8蛋白脂（酵母j亚基）将ATP6和ATP8锁在膜组件中，然后单体复合物通过ATP6亚基和6.8蛋白脂（j亚基）之间的相互作用二聚化。二聚体通过DAPIT（胰岛素敏感组织中的糖尿病相关蛋白；酵母亚基k）反向连接在一起，沿着嵴边缘形成长低聚物。
The ATP synthase in human mitochondria is a membrane-bound assembly of 29 proteins of 18 kinds. All but two membrane components are encoded in nuclear genes, synthesized on cytoplasmic ribosomes, and imported into the matrix of the organelle, where they are assembled into the complex with ATP6 and ATP8, the products of overlapping genes in mitochondrial DNA. Disruption of individual human genes for the nuclear-encoded subunits in the membrane portion of the enzyme leads to the formation of intermediate vestigial ATPase complexes that provide a description of the pathway of assembly of the membrane domain. The key intermediate complex consists of the F-1-c8 complex inhibited by the ATPase inhibitor protein IF1 and attached to the peripheral stalk, with subunits e, f, and g associated with the membrane domain of the peripheral stalk. This intermediate provides the template for insertion of ATP6 and ATP8, which are synthesized on mitochondrial ribosomes. Their association with the complex is stabilized by addition of the 6.8 proteolipid, and the complex is coupled to ATP synthesis at this point. A structure of the dimeric yeast F-o membrane domain is consistent with this model of assembly. The human 6.8 proteolipid (yeast j subunit) locks ATP6 and ATP8 into the membrane assembly, and the monomeric complexes then dimerize via interactions between ATP6 subunits and between 6.8 proteolipids (j subunits). The dimers are linked together back-to-face by DAPIT (diabetes-associated protein in insulin-sensitive tissue; yeast subunit k), forming long oligomers along the edges of the cristae.