2YLM

Mechanism of USP7 (HAUSP) activation by its C-terminal ubiquitin-like domain (HUBL) and allosteric regulation by GMP-synthetase.

2YLM の概要

• エントリーDOI: 10.2210/pdb2ylm/pdb
• 関連するPDBエントリー: 1NB8 1NBF 2F1W 2F1X 2F1Y 2F1Z 2FOJ 2FOO 2FOP 2XXN
• 分子名称: UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 7, CHLORIDE ION (3 entities in total)
• 機能のキーワード: hydrolase, ubl
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus: Q93009
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 61964.89

構造登録者

Faesen, A.C.,Perrakis, A.,Sixma, T.K. (登録日: 2011-06-03, 公開日: 2011-10-19, 最終更新日: 2024-05-08)

主引用文献

Faesen, A.C.,Dirac, A.M.G.,Shanmugham, A.,Ovaa, H.,Perrakis, A.,Sixma, T.K.
Mechanism of Usp7/Hausp Activation by its C- Terminal Ubiquitin-Like Domain and Allosteric Regulation by Gmp-Synthetase
Mol.Cell, 44:147-, 2011

PubMed Abstract: The ubiquitin-specific protease USP7/HAUSP regulates p53 and MDM2 levels, and cellular localization of FOXO4 and PTEN, and hence is critically important for their role in cellular processes. Here we show how the 64 kDa C-terminal region of USP7 can positively regulate deubiquitinating activity. We present the crystal structure of this USP7/HAUSP ubiquitin-like domain (HUBL) comprised of five ubiquitin-like (Ubl) domains organized in 2-1-2 Ubl units. The last di-Ubl unit, HUBL-45, is sufficient to activate USP7, through binding to a "switching" loop in the catalytic domain, which promotes ubiquitin binding and increases activity 100-fold. This activation can be enhanced allosterically by the metabolic enzyme GMPS. It binds to the first three Ubl domains (HUBL-123) and hyperactivates USP7 by stabilization of the HUBL-45-dependent active state.

PubMed: 21981925
DOI: 10.1016/J.MOLCEL.2011.06.034

実験手法

X-RAY DIFFRACTION (2.7 Å)