5K1B

Crystal structure of the UAF1/USP12 complex in F222 space group

5K1B の概要

• エントリーDOI: 10.2210/pdb5k1b/pdb
• 関連するPDBエントリー: 5K16 5K19 5K1A 5K1C
• 分子名称: WD repeat-containing protein 48, Ubiquitin carboxyl-terminal hydrolase 12, ZINC ION (3 entities in total)
• 機能のキーワード: wd40 domain, sumo-like domain, ubiquitin-specific protease 12, usp12, usp1-associated factor 1, deubiquitinating enzyme, dub, protein binding-hydrolase complex, protein binding/hydrolase
• 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: 118918.06

構造登録者

Li, H.,D'Andrea, A.D.,Zheng, N. (登録日: 2016-05-18, 公開日: 2016-07-20, 最終更新日: 2024-11-06)

主引用文献

Li, H.,Lim, K.S.,Kim, H.,Hinds, T.R.,Jo, U.,Mao, H.,Weller, C.E.,Sun, J.,Chatterjee, C.,D'Andrea, A.D.,Zheng, N.
Allosteric Activation of Ubiquitin-Specific Proteases by beta-Propeller Proteins UAF1 and WDR20.
Mol.Cell, 63:249-260, 2016

PubMed Abstract: Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms. Here we report on a series of crystallographic and biochemical analyses of an evolutionarily conserved deubiquitinase, USP12, which is activated by two β-propeller proteins, UAF1 and WDR20. Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far from its catalytic center. Without increasing the substrate affinity of USP12, the two β-propeller proteins potentiate the enzyme through different allosteric mechanisms. UAF1 docks at the distal end of the USP12 Fingers domain and induces a cascade of structural changes that reach a critical ubiquitin-contacting loop adjacent to the catalytic cleft. By contrast, WDR20 anchors at the base of this loop and remotely modulates the catalytic center of the enzyme. Our results provide a mechanistic example for allosteric activation of USPs by their regulatory partners.

PubMed: 27373336
DOI: 10.1016/j.molcel.2016.05.031

実験手法

X-RAY DIFFRACTION (3.3 Å)