猪心肌线粒体ATP合成酶c亚基的拓扑结构与生物力学特性

As the core enzyme of organism, mitochondrial ATP synthase can catalyzes the synthesis of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate (Pi), its structure and catalytic function exception will directly caused the abnormalities of mitochondrial metabolic function, and further leading to cardiac aging and decreasing heart function.. Firstly, the project will use the LB technique to assemble ATP synthase c subunit from swine myocardial mitochondria into the phospholipid membrane, in order to understand of the interaction between membrane molecules, and transfer the assembled monolayer onto mica for further structural analysis and mechanical measurements.. Secondly, high-resolution AFM will be applied to collect the topographical and mechanical characteristics of subunit c aggregates in phospholipid membrane; particularly concerns would be focused on the number of c subunits and the measurement of the binding forces among c subunits, γ subunits, and phospholipid molecules.. Finally, the combination of the AFM, the LB films of the research data, methods in biostatistics, theoretical physics and mechanics would be used to find the correlation function of topology structure, mechanical properties and catalytic function of ATP synthase subunit c, in order to resolve the mechanic and stoichiometry problems in the ATP synthesis of the ATP synthase. . Further studies on the topological and biomechanical properties of Myocardial mitochondrial ATP synthase will improve the understanding the pathogenesis in cardiac aging and heart dysfunction in mitochondrial molecular level.

线粒体ATP合成酶能催化合成ATP，是生物体能量转换的核心酶，其结构和催化功能的异常将直接引起线粒体代谢功能的紊乱，进而导致心肌衰老与心功能下降。本项目首先采用LB膜技术将猪心肌线粒体ATP合成酶c亚基组装到磷脂膜上，整体了解膜分子间的相互作用，并将组装膜转移至云母上以供结构分析和力学测量；其次，应用AFM高分辨成像和力学测量技术研究磷脂膜上c亚基聚集体的拓扑结构和生物力学特性，特别关注c亚基个数，并测量c亚基多聚体和γ亚基、c亚基间及其与磷脂分子间的结合力；最后，结合AFM、LB膜的研究数据，用生物统计和理论物理/力学的方法找到ATP合成酶c亚基拓扑结构、力学特性与催化功能间的函数关系，从而解决ATP合成酶催化合成ATP过程中的力学和化学计量问题。心肌线粒体ATP合成酶拓扑结构和生物力学特性的深入研究将有助于人们了解心肌衰老与心功能下降在线粒体分子层面的致病机理。

本项目采用LB膜技术将猪心肌线粒体ATP合成酶c亚基组装到磷脂膜上，研究了膜分子间的相互作用，并将组装膜转移至云母上以供结构分析和力学测量；应用AFM高分辨成像和力学测量技术研究磷脂膜上c亚基聚集体的拓扑结构和生物力学特性，特别关注了c亚基个数，并测量c亚基多聚体和γ亚基、c亚基间及其与磷脂分子间的结合力；结合AFM、LB膜的研究数据，用生物统计和理论物理/力学的方法找到ATP合成酶c亚基拓扑结构、力学特性与催化功能间的函数关系，从而解决ATP合成酶催化合成ATP过程中的力学和化学计量问题。心肌线粒体ATP合成酶拓扑结构和生物力学特性的深入研究将有助于人们了解心肌衰老与心功能下降在线粒体分子层面的致病机理。