2f1x: Difference between revisions
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'''Crystal structure of the TRAF-like domain of HAUSP/USP7 bound to a p53 peptide''' | {{Structure | ||
|PDB= 2f1x |SIZE=350|CAPTION= <scene name='initialview01'>2f1x</scene>, resolution 2.3Å | |||
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'''Crystal structure of the TRAF-like domain of HAUSP/USP7 bound to a p53 peptide''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2F1X is a [ | 2F1X is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F1X OCA]. | ||
==Reference== | ==Reference== | ||
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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16402859 16402859] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: usp7]] | [[Category: usp7]] | ||
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Revision as of 17:47, 20 March 2008
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Crystal structure of the TRAF-like domain of HAUSP/USP7 bound to a p53 peptide
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.
DiseaseDisease
Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[191170], Breast cancer OMIM:[191170], Colorectal cancer OMIM:[191170], Hepatocellular carcinoma OMIM:[191170], Histiocytoma OMIM:[191170], Li-Fraumeni syndrome OMIM:[191170], Multiple malignancy syndrome OMIM:[191170], Nasopharyngeal carcinoma OMIM:[191170], Osteosarcoma OMIM:[191170], Pancreatic cancer OMIM:[191170], Thyroid carcinoma OMIM:[191170]
About this StructureAbout this Structure
2F1X is a Single protein structure of sequence from Homo sapiens. 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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