线粒体内膜膜蛋白结构研究的新方法及应用

New Methods and Applications in the Research of Mitochondrial Inner Membrane Protein Structure

线粒体是细胞内极其重要的细胞器。一方面作为细胞的能量工厂,提供ATP来满足细胞的各种活动需要;另一方面,作为细胞内信号传导的节点,调控细胞内许多重要的生理进程。因此线粒体的功能紊乱直接导致多种重大疾病,对线粒体的研究是我国医学健康领域的重大需求。线粒体内膜如何进行跨膜信号传导,从而完成各项生理学功能,这方面的研究工作还比较缺乏。本项目旨在研究和发展新方法,改善长期困扰真核膜蛋白表达和纯化的瓶颈,力争探索出一条适合于实验室常规应用的真核膜蛋白表达纯化的路径。并在膜蛋白结构研究的三大主要技术——X-射线晶体衍射、生物冷冻电镜和核磁共振的现有基础上,开发和利用新技术和新方法,对具有重大生理功能的线粒体内膜膜蛋白质开展结构生物学和生理学功能研究,阐明线粒体跨内膜信号传导的科学问题。

Mitochondria are crucial cell organelle. As a cellular energy factory, they provide ATP for various cellular activities; On the other hand, as a cellular signaling node, they regulate many important physiological processes. Therefore, malfunctional mitochondria result in many vital diseases. It is urgent to carry out decent researches towards mitochondria for the requirement of national medical health improvement. How does various cellular signals transduce across inner membrane of mitochondria and mediate all kinds of activities？ It is poorly understood. Development and improvement of new technology, aiming to break the bottle neck problem during the expression and purification of eukaryotic membrane protein, builds a platform of eukaryotic membrane protein expression and purification suitable for regular laboratory. Based on current three major techniques to study membrane protein structure： x-ray crystallography, cryo electron microscopy and nuclear magnetic resonance, we are going to develop new technology and new methodology for studying structural and physiological function of mitochondrial inner membrane protein in order to eventually undercover the scientific question of transducing signal across mitochondrial inner membrane.