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PDBsum entry 2h9m
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Structural genomics, gene regulation
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PDB id
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2h9m
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References listed in PDB file
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Key reference
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Title
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Structural basis for molecular recognition and presentation of histone h3 by wdr5.
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Authors
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A.Schuetz,
A.Allali-Hassani,
F.Martín,
P.Loppnau,
M.Vedadi,
A.Bochkarev,
A.N.Plotnikov,
C.H.Arrowsmith,
J.Min.
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Ref.
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EMBO J, 2006,
25,
4245-4252.
[DOI no: ]
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PubMed id
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Abstract
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Histone methylation at specific lysine residues brings about various downstream
events that are mediated by different effector proteins. The WD40 domain of WDR5
represents a new class of histone methyl-lysine recognition domains that is
important for recruiting H3K4 methyltransferases to K4-dimethylated histone H3
tail as well as for global and gene-specific K4 trimethylation. Here we report
the crystal structures of full-length WDR5, WDR5Delta23 and its complexes with
unmodified, mono-, di- and trimethylated histone H3K4 peptides. The structures
reveal that WDR5 is able to bind all of these histone H3 peptides, but only
H3K4me2 peptide forms extra interactions with WDR5 by use of both water-mediated
hydrogen bonding and the altered hydrophilicity of the modified lysine 4. We
propose a mechanism for the involvement of WDR5 in binding and presenting
histone H3K4 for further methylation as a component of MLL complexes.
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Figure 4.
Figure 4 Interaction between WDR5 and histone peptides. (A)
H3K4me2 peptide is shown in a stick model colored in yellow, and
residues in WDR5 that make hydrogen bonds with H3K4me2 are also
shown in a stick model and colored in blue. Hydrogen bonds are
denoted as orange dotted lines. (B) Interaction of different
states of H3K4 with Glu322 in WDR5. Dimethylated K4 is shown as
a stick model colored in yellow, which interacts with Glu322 in
WDR5, colored in yellow, via a water molecule. Unmodified K4 in
the WDR5–H3K4 complex is colored in cyan, which is stabilized
by crystal contacts. The side chain of Glu322 in this complex is
either disordered or points to solvent. In the WDR5  23–H3K4me
complex structure, the side chain of K4me is disordered. The
side chain of Glu322 is either disordered or adopts the
conformation of Glu322 in the WDR5 23–H3K4me2
complex. K4me3 in the WDR5–H3K4me3 complex is disordered, and
Glu322, colored in magenta, points to solvent.
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Figure 5.
Figure 5 Detailed interaction between me2K4 in H3K4me2 and
Glu322 in WDR5. (A) The H3K4me2 peptide and WDR5 are colored in
yellow and blue, respectively. The electron density map is
contoured at 1  .
Potential water-mediated hydrogen bonds are shown as dashed
orange lines. (B) The lower panel shows schematics of two
alternative hydrogen binding networks involving the water
molecule.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
EMBO J
(2006,
25,
4245-4252)
copyright 2006.
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