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PDBsum entry 2k2d
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Metal binding protein
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PDB id
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2k2d
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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 basis of pirh2-Mediated p53 ubiquitylation.
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Authors
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Y.Sheng,
R.C.Laister,
A.Lemak,
B.Wu,
E.Tai,
S.Duan,
J.Lukin,
M.Sunnerhagen,
S.Srisailam,
M.Karra,
S.Benchimol,
C.H.Arrowsmith.
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Ref.
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Nat Struct Biol, 2008,
15,
1334-1342.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Pirh2 (p53-induced RING-H2 domain protein; also known as Rchy1) is an E3
ubiquitin ligase involved in a negative-feedback loop with p53. Using NMR
spectroscopy, we show that Pirh2 is a unique cysteine-rich protein comprising
three modular domains. The protein binds nine zinc ions using a variety of zinc
coordination schemes, including a RING domain and a left-handed beta-spiral in
which three zinc ions align three consecutive small beta-sheets in an
interleaved fashion. We show that Pirh2-p53 interaction is dependent on the
C-terminal zinc binding module of Pirh2, which binds to the tetramerization
domain of p53. As a result, Pirh2 preferentially ubiquitylates the tetrameric
form of p53 in vitro and in vivo, suggesting that Pirh2 regulates protein
turnover of the transcriptionally active form of p53.
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Figure 2.
(a) Pirh2 NTD. N lobe shows the interleaved Zn1 and Zn2 sites
and a four-cysteine-coordinated Zn3 site. C lobe shows
left-handed  -spiral
structure with three CCHC motifs coordinating Zn4, Zn5 and Zn6.
(b) Pirh2 RING domain, showing the interleaved Zn7 and Zn8
sites. (c) Pirh2 CTD, showing Zn9 site coordinated by four
cysteines. The nine zinc atoms are shown as spheres.
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Figure 7.
Top, domains of tetrameric p53 interacting with those of
Pirh2. UBE2D2-Pirh2 RING domain orientations are based on the
crystal structure of the homologous complex formed between UBCH7
and the c-Cbl RING domain^20. Bottom, active site cysteine of
UBE2D2, charged with ubiquitin, is shown in red.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2008,
15,
1334-1342)
copyright 2008.
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