Molecular analysis of the dimeric F1/F0-ATP synthase

二聚体 F1/F0-ATP 合酶的分子分析

• 批准号: 6620675
• 负责人: ROSEMARY A STUART
• 金额: $ 19.01万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620675
• 关键词: binding sites; chromatography; crosslink; cytochrome oxidase; dimer; enzyme inhibitors; fungal genetics; fungal proteins; hydrogen transporting ATP synthase; intermolecular interaction; model design /development; molecular assembly /self assembly; physical model; protein purification; protein structure function; stoichiometry; western blottings

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.

描述：（由申请人提供）我们最近表明，酵母 F1 F0-ATP合成酶复合物以二聚体形式存在于线粒体内， 膜的二聚体AlP合酶复合物的分离导致 鉴定了复合物的三个新亚基。这些亚基，Su e，Su g 和Su k被发现与二聚体形式的 ATP合成酶复合物。本建议的重点是了解 ATP合成酶二聚体的形成和功能。苏娥似乎扮演一个 在二聚ATP合酶的形成中起中心作用。了解两者 Su e和另一个二聚体的功能和排列 F0区的特定亚基代表了本研究的主要目标， 研究提案。其次，我们希望分析是否存在二聚体形式 F1 F0-ATP酶复合物在其被抑制的能力中起着核心作用。 天然抑制蛋白IF 1。最近的研究表明， ATP酶的天然抑制蛋白IF 1（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 无论是由Su e和Su g介导的二聚体F1 F0-ATP合酶的形成， 在保持相邻的F1扇区靠近每个扇区中起作用 其它的，以便能够结合抑制剂蛋白二聚体。最后我们 初步数据表明，ATP合酶二聚体的形成是 对于细胞色素氧化酶复合物的最大活性很重要。的 分析二聚ATP合酶的作用和可能参与 还提出了细胞色素氧化酶复合物。自大会以来， 预计这两种复合物的低聚状态在所有情况下都是相似的。 从这些研究中获得的信息应该有助于 未来的分析人类疾病源于酶的缺乏， F1 F0-ATP合酶或细胞色素氧化酶复合物。