Molecular analysis of the dimeric F1/F0-ATP synthase

描述：(申请人提供)我们最近证明了酵母 F1F0-ATP合成酶复合体以二聚体形式存在于线粒体内部 薄膜。二聚体ALP合成酶复合体的分离导致 鉴定了该复合体的三个新亚基。这些亚单位，苏e，苏g 和SU k被发现与二聚体形式的 三磷酸腺苷合成酶复合体。本提案的重点是了解 三磷酸腺苷合成酶二聚体的形成和功能。苏娥似乎在扮演一位 在二聚体三磷酸腺苷合成酶的形成中起中心作用。了解两者 苏e和其他二聚体的功能和排列 F0扇区内的特定亚基代表了这一主要目标 研究提案。其次，我们想要分析的是二聚体形式的 F1F0-ATPase复合体在其被抑制的能力中起着核心作用 天然抑制蛋白，IF1。最近已经证明， ATPase天然抑制蛋白IF1(在酵母中称为INH 1)形成 二聚体，并同时结合两个相邻的F1结构域。我们将分析 苏娥和苏格介导的二聚体F1F0-ATP合酶的形成， 在保持相邻的F1-扇区紧密相连方面发挥了作用 其他，从而使抑制蛋白二聚体能够结合。最后，我们的 初步数据表明，ATP合成酶二聚体的形成是 对细胞色素氧化酶复合体的最大活性很重要。这个 二聚体三磷酸腺苷合成酶的作用分析及其可能参与的 还提出了细胞色素氧化酶络合物的概念。由于大会和 预计这两种络合物的低聚状态都是相似的 对于真核生物，从这些研究中获得的信息应该有助于 酶缺乏引起的人类疾病的未来分析 F1F0-ATP合成酶或细胞色素氧化酶复合体。

DESCRIPTION: (provided by applicant) We have recently shown that the yeast F1F0-ATP synthase complex exists as a dimer in the mitochondrial inner membrane. Isolation of the dimeric AlP synthase complex led to the identification of three new subunits of the complex. These subunits, Su e, Su g and Su k were found to be specifically associated with the dimeric form of the ATP synthase complex. The present proposal focuses on understanding the formation and function of the ATP synthase dimer. Su e appears to play a central role in the formation of the dimeric ATP synthase. Understanding both the function and the arrangement of Su e, and the other dimer specific-subunits, within the F0-sector represents a major goal of this research proposal. Second, we wish to analyze if the dimeric form of the F1F0-ATPase complex plays a central role in its ability to be inhibited by the natural inhibitor protein, IF1. It has been recently demonstrated that the natural inhibitor protein of the ATPase, IF1 (termed INH 1 in yeast) forms dimers and binds two neighboring F1-domains, concomitantly. We shall analyze whether formation of the dimeric F1F0-ATP synthase, mediated by Su e and Su g, plays a role in maintaining neighboring F1-sectors in close proximity to each other, so as to enable binding of the inhibitor protein dimer. Finally, our preliminary data suggests that the formation of the ATP synthase dimer is important for the maximal activity of the cytochrome oxidase complex. The analysis of the role of the dimeric ATP synthase and possible involvement with the cytochrome oxidase complex is also proposed. Since the assembly and oligomeric state of both of these complexes is anticipated to be similar in all eukaryotes, information gained from these studies should be helpful in the future analysis of human disorders stemming from enzymatic deficiencies in either the F1F0-ATP synthase or cytochrome oxidase complexes.