2f1z: Difference between revisions

Revision as of 03:22, 4 May 2008

Crystal structure of HAUSP

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. 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 Page seeded by OCA on Sun May 4 03:22:01 2008

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OCA

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 [[Image:2f1z.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_2f1z", creates the "Structure Box" on the page.
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+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND=
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= USP7, HAUSP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2f1z|  PDB=2f1z  |  SCENE=  }}
-|RELATEDENTRY=[[2f1w|2F1W]], [[2f1x|2F1X]], [[2f1y|2F1Y]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f1z OCA], [http://www.ebi.ac.uk/pdbsum/2f1z PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2f1z RCSB]</span>
-}}
 '''Crystal structure of HAUSP'''
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 [[Category: Jeffrey, P D.]]
 [[Category: Shi, Y.]]
-[[Category: deubiquitinating enzyme]]
+[[Category: Deubiquitinating enzyme]]
-[[Category: hausp]]
+[[Category: Hausp]]
-[[Category: substrate recognition]]
+[[Category: Substrate recognition]]
-[[Category: ubp]]
+[[Category: Ubp]]
-[[Category: usp7]]
+[[Category: Usp7]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 03:22:01 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:56:48 2008''