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PDBsum entry 2dx8
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Metal binding protein
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PDB id
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2dx8
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References listed in PDB file
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Key reference
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Title
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Crystal structure analysis of the phd domain of the transcription co-Activator pygopus.
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Authors
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Y.Nakamura,
T.Umehara,
H.Hamana,
Y.Hayashizaki,
M.Inoue,
T.Kigawa,
M.Shirouzu,
T.Terada,
A.Tanaka,
B.Padmanabhan,
S.Yokoyama.
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Ref.
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J Mol Biol, 2007,
370,
80-92.
[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 were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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The Wnt/beta-catenin signaling pathway plays important roles in animal
development and cancer. Pygopus (Pygo) and Legless (Lgs) are recently discovered
core components of the Wnt/beta-catenin transcription machinery complex, and are
crucially involved in the regulation of the transcription of the
Arm/beta-catenin and T cell factors (TCF). Lgs/Bcl9 functions as an adaptor
between Pygo and Arm/beta-catenin. Here, we report the first crystal structure
of the plant homeodomain (PHD) finger of Pygopus (Pygo1 PHD), a Pygo family
member, which is essential for the association with Lgs/Bcl9. The Pygo1 PHD
structure forms a canonical PHD finger motif, stabilized by two Zn ions
coordinated in a cross-brace scheme. Surprisingly, the Pygo1 PHD domain forms a
dimer in both the crystals and solution. This is the first structural evidence
for dimerization among the known PHD domain structures. The dimer formation
occurs by the interactions of antiparallel beta-sheets between the
symmetry-related beta3 strands of the monomers. The Pygo1 PHD dimer interface
mainly comprises hydrophobic residues. Interestingly, some of the interface
residues, such as Met372, Thr373, Ala376 and Leu380, are reportedly important
for the association with Lgs/Bcl9 and are also critical for transcriptional
activation. The M372A and L380D mutants, and several surrounding mutants such as
S385A and A386D, showed decreased ability to form dimers and to interact with
the homology domain 1 (HD1) of Lgs/Bcl9. These results suggest that the Pygo1
PHD dimerization is functionally important for Lgs/Bcl9 recognition as well as
for the regulation of the Wnt/beta-catenin signaling pathway.
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Figure 2.
Figure 2. Tertiary structure of the mouse Pygo1 PHD domain. (a)
A representation of the electron density map. A section of the
final σ (a)-weighted 2F[o]-F[c] map at 2.8 Å resolution,
contoured at 1.0σ. (b) Ribbon representation of the mouse
Pygo1 PHD domain (blue to red). The two zinc ions, Zn1 and Zn2,
are shown as blue spheres, and the residues participating in
the Zn coordination system, as well as the conserved Trp388,
are shown as stick models. Structural Figures were generated
with PyMOL (ver. 0.99) [www.pymol.org]. Figure 2. Tertiary
structure of the mouse Pygo1 PHD domain. (a) A representation of
the electron density map. A section of the final σ (a)-weighted
2F[o]-F[c] map at 2.8 Å resolution, contoured at 1.0σ.
(b) Ribbon representation of the mouse Pygo1 PHD domain (blue to
red). The two zinc ions, Zn1 and Zn2, are shown as blue spheres,
and the residues participating in the Zn coordination system, as
well as the conserved Trp388, are shown as stick models.
Structural Figures were generated with PyMOL (ver. 0.99)
[www.pymol.org].
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Figure 6.
Figure 6. A comparison of the Pygo1 PHD domain with the ING2
and BPTF PHD domains. (a) A superposition of the Pygo1 PHD
domain (pink) onto the ING2 (green) and BPTF (cyan) PHD domains
complexed with the H3K4me3 histone peptides. The H3K4me3
peptides are shown by stick models and the trimethylated lysines
are labeled. (b) A representative electrostatic surface
potential of the ING2 complex. The H3K4me3 peptide is shown by a
stick model. (c) An electrostatic surface potential of the
Pygo1 PHD domain (chain A only) near the H3K4me3 binding
region. Panels (b) and (c) are in the same orientation as in
(a). The surfaces are colored blue and red for positive and
negative electrostatic surface potential, respectively.
Figure 6. A comparison of the Pygo1 PHD domain with the ING2 and
BPTF PHD domains. (a) A superposition of the Pygo1 PHD domain
(pink) onto the ING2 (green) and BPTF (cyan) PHD domains
complexed with the H3K4me3 histone peptides. The H3K4me3
peptides are shown by stick models and the trimethylated lysines
are labeled. (b) A representative electrostatic surface
potential of the ING2 complex. The H3K4me3 peptide is shown by a
stick model. (c) An electrostatic surface potential of the Pygo1
PHD domain (chain A only) near the H3K4me3 binding region.
Panels (b) and (c) are in the same orientation as in (a). The
surfaces are colored blue and red for positive and negative
electrostatic surface potential, respectively.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
370,
80-92)
copyright 2007.
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