RT Journal Article
SR Electronic
T1 Conformational landscape of the p28-bound human proteasome regulatory particle
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 088492
DO 10.1101/088492
A1 Ying Lu
A1 Jiayi Wu
A1 Shuobing Chen
A1 Shuangwu Sun
A1 Yong-Bei Ma
A1 Qi Ouyang
A1 Daniel Finley
A1 Marc W. Kirschner
A1 Youdong Mao
YR 2016
UL http://biorxiv.org/content/early/2016/11/19/088492.abstract
AB 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. We determined a cryo-EM structure of the human RP in complex with its assembly chaperone p28 at 4.5-Å resolution. The Rpn1-p28-AAA subcomplex in the p28-bound RP is highly dynamic and was resolved to subnanometer resolution in seven states, which recapitulate the conformational landscape of the complex. Surprisingly, the p28-bound AAA ring does not form a channel in the free RP. Instead, it spontaneously samples multiple ‘open’ and ‘closed’ topologies. Our analysis suggests that p28 guides the proteolytic core particle to select certain conformation of the ATPase ring for RP engagement in the last step of the chaperone-mediated proteasome assembly.