6HEH

Structure of the catalytic domain of USP28 (insertion deleted)

6HEH の概要

• エントリーDOI: 10.2210/pdb6heh/pdb
• 分子名称: Ubiquitin carboxyl-terminal hydrolase 28,Ubiquitin carboxyl-terminal hydrolase 28, 1,2-ETHANEDIOL, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: ubiquitin, usp, ubiquitin-specific protease, dub, deubiquitinase, protease, isopeptidase, usp28, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44684.21

構造登録者

Gersch, M.,Komander, D. (登録日: 2018-08-20, 公開日: 2019-03-27, 最終更新日: 2024-01-17)

主引用文献

Gersch, M.,Wagstaff, J.L.,Toms, A.V.,Graves, B.,Freund, S.M.V.,Komander, D.
Distinct USP25 and USP28 Oligomerization States Regulate Deubiquitinating Activity.
Mol.Cell, 74:436-, 2019

PubMed Abstract: The evolutionarily related deubiquitinating enzymes (DUBs) USP25 and USP28 comprise an identical overall domain architecture but are functionally non-redundant: USP28 stabilizes c-MYC and other nuclear proteins, and USP25 regulates inflammatory TRAF signaling. We here compare molecular features of USP25 and USP28. Active enzymes form distinctively shaped dimers, with a dimerizing insertion spatially separating independently active catalytic domains. In USP25, but not USP28, two dimers can form an autoinhibited tetramer, where a USP25-specific, conserved insertion sequence blocks ubiquitin binding. In full-length enzymes, a C-terminal domain with a previously unknown fold has no impact on oligomerization, but N-terminal regions affect the dimer-tetramer equilibrium in vitro. We confirm oligomeric states of USP25 and USP28 in cells and show that modulating oligomerization affects substrate stabilization in accordance with in vitro activity data. Our work highlights how regions outside of the catalytic domain enable a conceptually intriguing interplay of DUB oligomerization and activity.

PubMed: 30926242
DOI: 10.1016/j.molcel.2019.02.030

実験手法

X-RAY DIFFRACTION (2.26 Å)