毛有东
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毛有东
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论文成果
Structural basis for dynamic regulation of the human 26S proteasome
发布时间：2022-06-24点击次数：
影响因子：
9.6
DOI码：
10.1073/pnas.1614614113
发表刊物：
Proc Natl Acad Sci U S A
摘要：
The proteasome is the major engine of protein degradation in all eukaryotic cells. At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitylated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. Using cryoelectron microscopy, we determined a near-atomic-resolution structure of the 2.5-MDa human proteasome in its ground state, as well as subnanometer-resolution structures of the holoenzyme in three alternative conformational states. The substrate-unfolding AAA-ATPase channel is narrowed by 10 inward-facing pore loops arranged into two helices that run in parallel with each other, one hydrophobic in character and the other highly charged. The gate of the core particle was unexpectedly found closed in the ground state and open in only one of the alternative states. Coordinated, stepwise conformational changes of the regulatory particle couple ATP hydrolysis to substrate translocation and regulate gating of the core particle, leading to processive degradation.
论文类型：
期刊论文
学科门类：
理学
文献类型：
J
卷号：
113
期号：
46
页面范围：
12991-12996
是否译文：
否
发表时间：
2016-11-15
收录刊物：
SCI