2F1W

Crystal structure of the TRAF-like domain of HAUSP/USP7

Summary for 2F1W

• Entry DOI: 10.2210/pdb2f1w/pdb
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 7, CALCIUM ION (3 entities in total)
• Functional Keywords: ubp, traf-like domain, substrate binding, hausp, usp7, p53 recognition, mdm2 recognition, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q93009
• Total number of polymer chains: 1
• Total formula weight: 18573.64

Authors

Hu, M.,Gu, L.,Jeffrey, P.D.,Shi, Y. (deposition date: 2005-11-15, release date: 2006-02-07, Last modification date: 2024-02-14)

Primary citation

Hu, M.,Gu, L.,Li, M.,Jeffrey, P.D.,Gu, W.,Shi, Y.
Structural Basis of Competitive Recognition of p53 and MDM2 by HAUSP/USP7: Implications for the Regulation of the p53-MDM2 Pathway.
Plos Biol., 4:e27-e27, 2006

PubMed Abstract: Herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7), a deubiquitylating enzyme of the ubiquitin-specific processing protease family, specifically deubiquitylates both p53 and MDM2, hence playing an important yet enigmatic role in the p53-MDM2 pathway. Here we demonstrate that both p53 and MDM2 specifically recognize the N-terminal tumor necrosis factor-receptor associated factor (TRAF)-like domain of HAUSP in a mutually exclusive manner. HAUSP preferentially forms a stable HAUSP-MDM2 complex even in the presence of excess p53. The HAUSP-binding elements were mapped to a peptide fragment in the carboxy-terminus of p53 and to a short-peptide region preceding the acidic domain of MDM2. The crystal structures of the HAUSP TRAF-like domain in complex with p53 and MDM2 peptides, determined at 2.3-A and 1.7-A resolutions, respectively, reveal that the MDM2 peptide recognizes the same surface groove in HAUSP as that recognized by p53 but mediates more extensive interactions. Structural comparison led to the identification of a consensus peptide-recognition sequence by HAUSP. These results, together with the structure of a combined substrate-binding-and-deubiquitylation domain of HAUSP, provide important insights into regulation of the p53-MDM2 pathway by HAUSP.

PubMed: 16402859
DOI: 10.1371/journal.pbio.0040027

Experimental method

X-RAY DIFFRACTION (1.65 Å)