2f1z
Crystal structure of HAUSP
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OverviewOverview
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.
About this StructureAbout this Structure
2F1Z is a Single protein structure of sequence from Homo sapiens. Active as Ubiquitin thiolesterase, with EC number 3.1.2.15 Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway., Hu M, Gu L, Li M, Jeffrey PD, Gu W, Shi Y, PLoS Biol. 2006 Feb;4(2):e27. Epub 2006 Jan 17. PMID:16402859
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