3TMP

The catalytic domain of human deubiquitinase DUBA in complex with ubiquitin aldehyde

3TMP の概要

• エントリーDOI: 10.2210/pdb3tmp/pdb
• 関連するPDBエントリー: 3TMO
• 分子名称: OTU domain-containing protein 5, Polyubiquitin-C (3 entities in total)
• 機能のキーワード: otu fold, deubiquitinase, phosphorylation, hydrolase-protein binding complex, hydrolase/protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Ubiquitin: Cytoplasm (By similarity): P0CG48
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 119269.44

構造登録者

Ma, X.,Yin, J.,Hymowitz, S.,Starovasnik, M.,Cochran, A. (登録日: 2011-08-31, 公開日: 2012-01-11, 最終更新日: 2025-03-26)

主引用文献

Huang, O.W.,Ma, X.,Yin, J.,Flinders, J.,Maurer, T.,Kayagaki, N.,Phung, Q.,Bosanac, I.,Arnott, D.,Dixit, V.M.,Hymowitz, S.G.,Starovasnik, M.A.,Cochran, A.G.
Phosphorylation-dependent activity of the deubiquitinase DUBA.
Nat.Struct.Mol.Biol., 19:171-175, 2012

PubMed Abstract: Addition and removal of ubiquitin or ubiquitin chains to and from proteins is a tightly regulated process that contributes to cellular signaling and protein stability. Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. The crystal structure of the ubiquitin aldehyde adduct of active DUBA reveals a marked cooperation between phosphorylation and substrate binding. An intricate web of interactions involving the phosphate and the C-terminal tail of ubiquitin cause DUBA to fold around its substrate, revealing why phosphorylation is essential for deubiquitinase activity. Phosphoactivation of DUBA represents an unprecedented mode of protease regulation and a clear link between two major cellular signal transduction systems: phosphorylation and ubiquitin modification.

PubMed: 22245969
DOI: 10.1038/nsmb.2206

実験手法

X-RAY DIFFRACTION (1.91 Å)