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    目:A dynamic view on the design principle of human 26S proteasome machinery

报告人: Youdong Mao (毛有东)Ph.D.

Center for Quantitative Biology and School of Physics, Peking University



主持人:齐志 研究员


The proteasome is an ATP-dependent, 2.5-megadalton machine responsible for selective protein degradation in eukaryotic cells. In this talk, I will summarize our recent studies with cryo-EM on the structures and dynamics of both substrate-free and substrate-engaged human proteasome in a dozen of conformational states at near-atomic resolution. We will discuss how these structures visualize a continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to substrate translocation, during which ATP hydrolysis sequentially navigates through all six ATPases. Most importantly, three principal modes of coordinated hydrolysis are observed, featuring hydrolytic events in two oppositely positioned ATPases, in two adjacent ATPases, and in one ATPase at a time. These hydrolytic modes regulate deubiquitylation, translocation initiation and processive unfolding of substrates, respectively. ATP hydrolysis powers a hinge-like motion in each ATPase that regulates its substrate interaction. Synchronization of ATP binding, ADP release and ATP hydrolysis in three adjacent ATPases drives rigid-body rotations of substrate-bound ATPases that are propagated unidirectionally in the ATPase ring and unfold the substrate. Taken together, these studies reveal how proteasome dynamics elegantly regulate its function as well as the design principle of the proteasome machinery.


毛有东研究员1999年毕业于武汉大学物理学系,2005年获北京大学物理学院凝聚态专业博士学位。20052007年在国家纳米科学中心从事访问研究,20072012年在哈佛大学医学院Dana-Farber癌症研究所,从事博士后研究工作。2012-2015在哈佛大学医学院Dana-Farber癌症研究所担任讲师,创办并主持Intel并行计算结构生物学中心,担任研究员、主任,主持创建了哈佛的第一套Arctica高通量高分辨冷冻电镜平台。2015年初回到北京大学物理学院凝聚态所,任青年千人研究员,年底加入定量生物学中心任研究员,开展基于冷冻电子显微镜和高性能计算方法的结构系统生物学和生物物理动力学研究。相关成果发表在ScienceNature及子刊,PNASMol CellPLoS One等国际著名刊物上。