2foo
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The Crystal Strucure of the N-terminal domain of HAUSP/USP7 complexed with p53 peptide 359-362
OverviewOverview
The ubiquitin-specific protease, USP7, has key roles in the p53 pathway, whereby it stabilizes both p53 and MDM2. We show that the N-terminal, domain of USP7 binds two closely spaced 4-residue sites in both p53 and, MDM2, falling between p53 residues 359-367 and MDM2 residues 147-159., Cocrystal structures with USP7 were determined for both p53 peptides and, for one MDM2 peptide. These peptides bind the same surface of USP7 as, Epstein-Barr nuclear antigen-1, explaining the competitive nature of the, interactions. The structures and mutagenesis data indicate a preference, for a P/AXXS motif in peptides that bind USP7. Contacts made by serine are, identical and crucial for all peptides, and Trp165 in the peptide-binding, pocket of USP7 is also crucial. These results help to elucidate the, mechanism of substrate recognition by USP7 and the regulation of the p53, pathway.
About this StructureAbout this Structure
2FOO 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
Molecular recognition of p53 and MDM2 by USP7/HAUSP., Sheng Y, Saridakis V, Sarkari F, Duan S, Wu T, Arrowsmith CH, Frappier L, Nat Struct Mol Biol. 2006 Mar;13(3):285-91. Epub 2006 Feb 12. PMID:16474402
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