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PDBsum entry 2foj
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References listed in PDB file
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Key reference
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Title
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Molecular recognition of p53 and mdm2 by usp7/hausp.
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Authors
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Y.Sheng,
V.Saridakis,
F.Sarkari,
S.Duan,
T.Wu,
C.H.Arrowsmith,
L.Frappier.
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Ref.
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Nat Struct Mol Biol, 2006,
13,
285-291.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Figure 1. Crystal structure of USP7 NTD bound to p53 site
359-PGGS-362. (a) Transparent surface diagrams of p53–USP7.
(b) Detailed interactions between USP7 (light gray) and p53
(dark gray). (c) Overlay of p53 (red) and EBNA1 (green) peptides
from complex structures. (d) Overlay of p53 (red) and TRANCE-R
(yellow) peptides from complex structures, showing conserved
interactions with USP7 (purple) and TRAF6 (blue) residues.
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Figure 2.
Figure 2. Crystal structure of USP7 NTD bound to p53 site
364-AHSS-367. (a) Transparent surface diagram of USP7 NTD
bound by p53 mutant peptide 358-EAGGARAHSS-367 (blue). (b)
Detailed interactions between USP7 (light gray) and p53 (dark
gray). (c) Overlay of p53 peptides 359-PGGS-362 (red) and
364-AHSS-367 (turquoise) from USP7 complex structures.
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Figure 4.
Figure 4. Crystal structure of USP7 NTD bound to MDM2 peptide 4.
(a) Transparent surface diagram of MDM2-USP7. (b) Detailed
interactions between USP7 (light gray) and MDM2 (dark gray). (c)
Overlay of MDM2 (blue) and p53 359-PGGS-362 (red) peptides from
USP7 complex structures.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2006,
13,
285-291)
copyright 2006.
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