4UF5

Crystal structure of UCH-L5 in complex with inhibitory fragment of INO80G

4UF5 の概要

• エントリーDOI: 10.2210/pdb4uf5/pdb
• 分子名称: UBIQUITIN CARBOXYL-TERMINAL HYDROLASE ISOZYME L5, NUCLEAR FACTOR RELATED TO KAPPA-B-BINDING PROTEIN (2 entities in total)
• 機能のキーワード: hydrolase, deubiquitinating enzyme
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53498.64

構造登録者

Sahtoe, D.D.,Van Dijk, W.J.,El Oualid, F.,Ekkebus, R.,Ovaa, H.,Sixma, T.K. (登録日: 2014-12-23, 公開日: 2015-03-04, 最終更新日: 2023-12-20)

主引用文献

Sahtoe, D.D.,Van Dijk, W.J.,El Oualid, F.,Ekkebus, R.,Ovaa, H.,Sixma, T.K.
Mechanism of Uch-L5 Activation and Inhibition by Deubad Domains in Rpn13 and Ino80G.
Mol.Cell, 57:887-, 2015

PubMed Abstract: Deubiquitinating enzymes (DUBs) control vital processes in eukaryotes by hydrolyzing ubiquitin adducts. Their activities are tightly regulated, but the mechanisms remain elusive. In particular, the DUB UCH-L5 can be either activated or inhibited by conserved regulatory proteins RPN13 and INO80G, respectively. Here we show how the DEUBAD domain in RPN13 activates UCH-L5 by positioning its C-terminal ULD domain and crossover loop to promote substrate binding and catalysis. The related DEUBAD domain in INO80G inhibits UCH-L5 by exploiting similar structural elements in UCH-L5 to promote a radically different conformation, and employs molecular mimicry to block ubiquitin docking. In this process, large conformational changes create small but highly specific interfaces that mediate activity modulation of UCH-L5 by altering the affinity for substrates. Our results establish how related domains can exploit enzyme conformational plasticity to allosterically regulate DUB activity. These allosteric sites may present novel insights for pharmaceutical intervention in DUB activity.

PubMed: 25702870
DOI: 10.1016/J.MOLCEL.2014.12.039

実験手法

X-RAY DIFFRACTION (3.7 Å)