摘要
呼吸作用是生物体最基本最重要的生命活动。在哺乳动物中,呼吸作用(氧化磷酸化)由位于线粒体内膜上的呼吸链复合物完成。一百多年来,科学家们孜孜不倦地对线粒体呼吸链复合物进行研究,想要窥探这一能量大分子机器的全貌,但是一直未能获取该复合物蛋白质结构。我们最新的研究首次纯化出了来源于人类细胞的线粒体呼吸链超超级复合物Ⅰ_2Ⅲ_2Ⅳ_2,通过冷冻电镜技术首次成功解析了它的结构,并且提出呼吸链复合物Ⅰ、Ⅱ、Ⅲ和Ⅳ可以一起组成超大型复合物Ⅰ_2Ⅱ_2Ⅲ_2Ⅳ_2,这是呼吸链超超级复合物的终极形态。同时,我们所解析的人源呼吸链超级复合物的高分辨率结构,为攻克线粒体缺陷引起的阿尔兹海默综合征、帕金森综合征、多发性硬化、少年脊髓型共济失调以及肌萎缩性脊髓侧索硬化症等多种疾病打下了坚实的基础。
Respiration is one of the most vital and basic features of living organism. In mammals, respiration is accomplished by respiratory chain complexes located on mitochondrial inner membrane. In the past century, scientists have put tremendous efforts in understanding these complexes, but failed to solve the high resolution structure until recently. This year, our latest work purified megacomplex Ⅰ2Ⅲ2Ⅳ2 from cultured human cells for the first time around the world, and solved its sturcture using cryo-EM single particle analysis. Besides, with the help of computer stimulation, we propose complex Ⅱ is also involved in the megacomplex, which lead to the ultimate form Ⅰ2Ⅱ2Ⅲ2Ⅳ2. Definitely, our high resolution megacomplex structure will provide precious information for conquering the mitochondrial malfunction diseases, including Alzheimer＇s syndrome, Parkinson＇s disease, multiple sclerosis, friedreich＇s ataxia, Amyotrophic lateral sclerosis, etc.
作者
谷金科
宗帅
吴萌
郭润域
杨茂君
Gu Jinke;Zong Shuai;Wu Meng;Guo Runyu;Yang Maojun(Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China)
出处
《中国细胞生物学学报》
CAS
CSCD
2018年第4期463-469,共7页
Chinese Journal of Cell Biology
基金
国家蛋白质重大研究计划(批准号:2017YFA0504600
2016YFA0501100)
国家自然科学基金委杰出青年基金(批准号:31625008)
国家自然科学基金重点项目(批准号:21532004)和国家自然科学基金面上项目(批准号:31570733)资助的课题~~
