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

项目名称： 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

项目编号： No.11202170

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 朱杰

作者单位： 西北农林科技大学

项目金额： 28万元

中文摘要： 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。

中文关键词： 线粒体；ATP合成酶；磷脂；原子力显微镜；生物力学

英文摘要： 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

英文关键词： mitochondria；ATPase；phospholipid；atomic force microscopy；biomechanics