2YLM

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

Summary for 2YLM

• Entry DOI: 10.2210/pdb2ylm/pdb
• Related: 1NB8 1NBF 2F1W 2F1X 2F1Y 2F1Z 2FOJ 2FOO 2FOP 2XXN
• Descriptor: UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 7, CHLORIDE ION (3 entities in total)
• Functional Keywords: hydrolase, ubl
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus: Q93009
• Total number of polymer chains: 1
• Total formula weight: 61964.89

Authors

Faesen, A.C.,Perrakis, A.,Sixma, T.K. (deposition date: 2011-06-03, release date: 2011-10-19, Last modification date: 2024-05-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)