Paper Publications

Impact Factor:0.0

Journal:Molecular Cell

Abstract:The proteasome holoenzyme is activated by its regulatory particle (RP) consisting of two subcomplexes, the lid and the base. A key event in base assembly is the formation of a heterohexameric ring of AAA-ATPases, which is guided by at least four RP assembly chaperones in mammals: PAAF1, p28/gankyrin, p27/PSMD9, and S5b. Using cryogenic electron microscopy, we analyzed the non-AAA structure of the p28-bound human RP at 4.5 Å resolution and determined seven distinct conformations of the Rpn1-p28-AAA subcomplex within the p28-bound RP at subnanometer resolutions. Remarkably, the p28-bound AAA ring does not form a channel in the free RP and spontaneously samples multiple "open" and "closed" topologies at the Rpt2-Rpt6 and Rpt3-Rpt4 interfaces. Our analysis suggests that p28 assists the proteolytic core particle to select a specific conformation of the ATPase ring for RP engagement and is released in a shoehorn-like fashion in the last step of the chaperone-mediated proteasome assembly.

Indexed by:Journal paper

Discipline:Natural Science

Document Type:J

Volume:67

Issue:2

Page Number:322-333

Translation or Not:no

Date of Publication:2017-07-20

First Author:Ying Lu,Jiayi Wu

Correspondence Author:Marc W Kirschner,Youdong Mao

All the Authors:Yuanchen Dong,Shuobing Chen,Shuangwu Sun,Yong-Bei Ma,Qi Ouyang,Daniel Finley