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PDBsum entry 2vpe
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Gene regulation
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PDB id
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2vpe
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Contents |
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61 a.a.
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30 a.a.
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62 a.a.
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29 a.a.
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References listed in PDB file
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Key reference
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Title
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Decoding of methylated histone h3 tail by the pygo-Bcl9 wnt signaling complex.
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Authors
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M.Fiedler,
M.J.Sánchez-Barrena,
M.Nekrasov,
J.Mieszczanek,
V.Rybin,
J.Müller,
P.Evans,
M.Bienz.
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Ref.
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Mol Cell, 2008,
30,
507-518.
[DOI no: ]
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PubMed id
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Abstract
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Pygo and BCL9/Legless transduce the Wnt signal by promoting the transcriptional
activity of beta-catenin/Armadillo in normal and malignant cells. We show that
human and Drosophila Pygo PHD fingers associate with their cognate HD1 domains
from BCL9/Legless to bind specifically to the histone H3 tail methylated at
lysine 4 (H3K4me). The crystal structures of ternary complexes between PHD, HD1,
and two different H3K4me peptides reveal a unique mode of histone tail
recognition: efficient histone binding requires HD1 association, and the PHD-HD1
complex binds preferentially to H3K4me2 while displaying insensitivity to
methylation of H3R2. Therefore, this is a prime example of histone tail binding
by a PHD finger (of Pygo) being modulated by a cofactor (BCL9/Legless). Rescue
experiments in Drosophila indicate that Wnt signaling outputs depend on histone
decoding. The specificity of this process provided by the Pygo-BCL9/Legless
complex suggests that this complex facilitates an early step in the transition
from gene silence to Wnt-induced transcription.
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Figure 4.
Structures of the Ternary Complex, and H3K4me-Binding
Cavities (A) Molecular surface representation of hPHD-HD1
binding to H3K4me2 (in yellow cylinder style), with W366 and
other critical residues labeled. (B and C) Cylinder
representations of (B) semiaromatic K4me2 cavity and (C) A1
cavity, with critical H bonds indicated as dotted lines and
hydrophobic contacts as double brackets. (D) Molecular surface
representation of PHD, revealing solvent exposure of R2
(regardless of its methylation status). H3K4me, yellow; PHD
cavity residues, green. Note that Tern2 has essentially the same
structure as Tern1 (shown here; see text). (E) Binding constants
of various hPHD point mutants for H3K4me3 15-mer (K[d] values in
[mu]M; see also Figure 3 Figure 3- ).
Mol Cell. 2008 May 23; 30(4-2): 507–518. doi:
10.1016/j.molcel.2008.03.011. Copyright [copyright] 2008 ELL &
Excerpta Medica
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Figure 5.
Buttressing of the PHD A1 Cavity by HD1 (A) Molecular surface
representation of PHD (green) with electrostatic potential,
facing A1 cavity (left, yellow) and HD1 (right, orange). (B)
Buttressing of A1 cavity of PHD (molecular surface
representation with electrostatic potential) by HD1 (ribbon
representation). D352 lip residue of the K4me2 cavity and E360
residue critical for A1 anchoring are indicated. Mol Cell. 2008
May 23; 30(4-2): 507–518. doi: 10.1016/j.molcel.2008.03.011.
Copyright [copyright] 2008 ELL & Excerpta Medica
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Mol Cell
(2008,
30,
507-518)
copyright 2008.
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