Structure, mechanisms, regulation and assembly of ATP synthase

ATP合酶的结构、机制、调控和组装

• 批准号: MC_EX_MR/M009858/1
• 负责人: John Walker
• 金额: $ 317.9万
• 依托单位: MRC Centre Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_EX_MR%2FM009858%2F1
• 关键词: Structure; mechanisms; regulation; assembly; ATP

Biological life depends on a source of energy. That energy comes from sunlight. It is harvested by photosynthesis in green plants, and provides the high energy components in the foods that we eat. We harvest that energy in our bodies by "burning" (oxidising) the high energy components, releasing cellular energy in a controlled way to generate the fuel of life, in the form of the molecule known as adenosine triphosphate (or ATP for short). The key steps in this process take place in the mitochondria inside the cells that make up our tissues. The mitochondria are biological "power stations" full of millions of tiny molecular turbines, the ATP synthases, that rotate rather like man-made turbines churning out the cellular fuel in massive quantities, which is then delivered to all parts of our bodies to provide the energy to make them function. We understand in great detail many aspects of how these molecular turbines work, but as yet not how the rotary action is generated. Part of this project is about providing that crucial missing information. Bacteria have similar turbines that differ is some respects from the human turbines. We want to understand these differences better, so that we can devise drugs to kill pathogenic bacteria, such as the one that causes tuberculosis, by stopping their turbines without influencing the human ones. Associated with the human turbines, but not part of the ATP making machinery, is a channel that becomes opened, for example during a heart attack, letting out the contents of the mitochondria in an uncontrolled way leading to the death of the cell. We want to understand how this pore works, so that we can help design other drugs to control the pore.

生物的生命依赖于能量的来源。这种能量来自阳光。它是通过绿色植物的光合作用收获的，并为我们所吃的食物提供高能量成分。我们通过“燃烧”（氧化）高能量成分来收获体内的能量，以受控的方式释放细胞能量以产生生命的燃料，以被称为三磷酸腺苷（简称ATP）的分子的形式。这个过程中的关键步骤发生在构成我们组织的细胞内的线粒体中。线粒体是生物“发电站”，充满了数百万个微小的分子涡轮机（ATP合酶），它们像人造涡轮机一样旋转，大量生产细胞燃料，然后将其输送到我们身体的各个部位，提供能量使它们发挥作用。我们非常详细地了解了这些分子涡轮机如何工作的许多方面，但还不知道旋转动作是如何产生的。这个项目的一部分是关于提供关键的缺失信息。细菌有类似的涡轮机，不同的是一些方面从人类的涡轮机。我们希望更好地了解这些差异，这样我们就可以设计药物来杀死致病菌，比如导致肺结核的细菌，通过停止涡轮机而不影响人类的涡轮机。与人类涡轮机相关，但不是ATP制造机器的一部分，是一个通道，例如在心脏病发作期间打开，以不受控制的方式释放线粒体的内容物，导致细胞死亡。我们想了解这个毛孔是如何工作的，这样我们就可以帮助设计其他药物来控制毛孔。

项目成果

TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase and interact with assembly factors for complex I.

• DOI: 10.1073/pnas.2100558118
• 发表时间: 2021-03-30
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Carroll J;He J;Ding S;Fearnley IM;Walker JE
• 通讯作者: Walker JE