Gender:Male
Date of Birth:1977-04-06
Alma Mater:Peking University
Education Level:Postgraduate (Doctoral)
[MORE] Academic Honor:2021 Winner of National Science Fund for Distinguished Young Scholars
北京大学黄廷方／信和青年杰出学者奖
博雅青年学者奖
Impact Factor:49.0
DOI number:10.1038/s41586-018-0736-4
Journal:Nature
Abstract:The proteasome is an ATP-dependent, 2.5-megadalton molecular machine that is responsible for selective protein degradation in eukaryotic cells. Here we present cryo-electron microscopy structures of the substrate-engaged human proteasome in seven conformational states at 2.8-3.6 Å resolution, captured during breakdown of a polyubiquitylated protein. These structures illuminate a spatiotemporal continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to substrate translocation, during which ATP hydrolysis sequentially navigates through all six ATPases. There are three principal modes of coordinated hydrolysis, featuring hydrolytic events in two oppositely positioned ATPases, in two adjacent ATPases and in one ATPase at a time. These hydrolytic modes regulate deubiquitylation, initiation of translocation and processive unfolding of substrates, respectively. Hydrolysis of ATP 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.
Discipline:Natural Science
Document Type:J
Volume:565
Page Number:49-55
Translation or Not:no
Date of Publication:2018-11-12
Included Journals:SCI
First Author:Yuanchen Dong,Shuwen Zhang
Correspondence Author:Youdong Mao
All the Authors:Zhaolong Wu,Xuemei Li,Wei Li Wang,Yanan Zhu,Svetla Stoilova-McPhie,Ying Lu,Daniel Finley
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