3JCK

Structure of the yeast 26S proteasome lid sub-complex

3JCK の概要

• エントリーDOI: 10.2210/pdb3jck/pdb
• EMDBエントリー: 6479
• 分子名称: 26S proteasome regulatory subunit RPN3, ZINC ION, 26S proteasome regulatory subunit RPN5, ... (11 entities in total)
• 機能のキーワード: proteasome, deubiquitinase, rpn11, protein homeostasis, hydrolase
• 由来する生物種: Saccharomyces cerevisiae S288c (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 361332.06

構造登録者

Herzik Jr., M.A.,Dambacher, C.M.,Worden, E.J.,Martin, A.,Lander, G.C. (登録日: 2015-12-20, 公開日: 2016-01-20, 最終更新日: 2025-06-11)

主引用文献

Dambacher, C.M.,Worden, E.J.,Herzik, M.A.,Martin, A.,Lander, G.C.
Atomic structure of the 26S proteasome lid reveals the mechanism of deubiquitinase inhibition.
Elife, 5:e13027-e13027, 2016

PubMed Abstract: The 26S proteasome is responsible for the selective, ATP-dependent degradation of polyubiquitinated cellular proteins. Removal of ubiquitin chains from targeted substrates at the proteasome is a prerequisite for substrate processing and is accomplished by Rpn11, a deubiquitinase within the 'lid' sub-complex. Prior to the lid's incorporation into the proteasome, Rpn11 deubiquitinase activity is inhibited to prevent unwarranted deubiquitination of polyubiquitinated proteins. Here we present the atomic model of the isolated lid sub-complex, as determined by cryo-electron microscopy at 3.5 Å resolution, revealing how Rpn11 is inhibited through its interaction with a neighboring lid subunit, Rpn5. Through mutagenesis of specific residues, we describe the network of interactions that are required to stabilize this inhibited state. These results provide significant insight into the intricate mechanisms of proteasome assembly, outlining the substantial conformational rearrangements that occur during incorporation of the lid into the 26S holoenzyme, which ultimately activates the deubiquitinase for substrate degradation.

PubMed: 26744777
DOI: 10.7554/eLife.13027

実験手法

ELECTRON MICROSCOPY (3.5 Å)