2f1w: Difference between revisions
New page: left|200px<br /> <applet load="2f1w" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f1w, resolution 1.65Å" /> '''Crystal structure o... |
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[[Image:2f1w.gif|left|200px]]<br /> | [[Image:2f1w.gif|left|200px]]<br /><applet load="2f1w" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''Crystal structure of the TRAF-like domain of HAUSP/USP7'''<br /> | '''Crystal structure of the TRAF-like domain of HAUSP/USP7'''<br /> | ||
==Overview== | ==Overview== | ||
Herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as | 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 Structure== | ==About this Structure== | ||
2F1W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] Full crystallographic information is available from [http:// | 2F1W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F1W OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Gu, L.]] | [[Category: Gu, L.]] | ||
[[Category: Hu, M.]] | [[Category: Hu, M.]] | ||
[[Category: Jeffrey, P | [[Category: Jeffrey, P D.]] | ||
[[Category: Shi, Y.]] | [[Category: Shi, Y.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: usp7]] | [[Category: usp7]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:16:50 2008'' | ||
Revision as of 18:16, 21 February 2008
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Crystal structure of the TRAF-like domain of HAUSP/USP7
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
2F1W is a Single protein structure of sequence from Homo sapiens with as ligand. 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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