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Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome
发布时间:2020-03-10点击次数:
影响因子: 49.0
DOI码: 10.1038/s41586-018-0736-4
发表刊物: Nature
摘要: 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.
学科门类: 理学
文献类型: J
卷号: 565
页面范围: 49-55
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发表时间: 2018-11-12
收录刊物: SCI
第一作者: Yuanchen Dong
第一作者: Shuwen Zhang
通讯作者: Youdong Mao
合写作者: Zhaolong Wu
合写作者: Xuemei Li
合写作者: Wei Li Wang
合写作者: Yanan Zhu
合写作者: Svetla Stoilova-McPhie
合写作者: Ying Lu
合写作者: Daniel Finley