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PDBsum entry 2h14
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Transcription
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PDB id
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2h14
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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 histone h3 by the wd40 protein wdr5.
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Authors
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J.F.Couture,
E.Collazo,
R.C.Trievel.
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Ref.
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Nat Struct Mol Biol, 2006,
13,
698-703.
[DOI no: ]
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PubMed id
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Abstract
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The WD40-repeat protein WDR5 is a conserved subunit of Trithorax (TRX) histone
methyltransferase complexes. WDR5 has been reported to selectively bind
dimethylated Lys4 (K4me2) in histone H3 to promote K4 trimethylation by TRX. To
elucidate the basis of this binding specificity, we have determined the crystal
structure of WDR5 bound to a histone H3 peptide bearing K4me2. The structure
reveals that the N terminus of histone H3 binds as a 3(10)-helix in the central
depression formed by the WD40 repeats. R2 in histone H3 is bound in the acidic
channel in the protein's core, whereas K4me2 is solvent exposed and does not
engage in direct interactions with WDR5. Functional studies confirm that WDR5
recognizes A1, R2 and T3 in histone H3 but has virtually identical affinities
for the unmodified and mono-, di- and trimethylated forms of K4, demonstrating
that it does not discriminate among different degrees of methylation of this
residue.
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Figure 1.
Figure 1. Crystal structure of WDR5 bound to the N terminus of
histone H3. (a) Two orthogonal views of the secondary
structure of WDR5 with the  -propeller
blades and the N and C termini labeled. The distorted sixth -propeller
is highlighted in green, and the carbon atoms of the histone H3
peptide are rendered in yellow. (b) Electrostatic surface of
WDR5 showing the histone H3 binding cleft (blue and red denote
positively and negatively charged regions, respectively). The
histone H3 peptide is shown as in a.
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Figure 2.
Figure 2. Recognition of the histone H3 N terminus by WDR5.
(a) Stereo view of the simulated annealing F[o] - F[c] omit map
(green). Electron density is contoured at 2.0  .
Gray carbons, WDR5; yellow carbons, histone H3. Q5 in histone H3
was omitted from the image for clarity. (b) Schematic
representation of the interactions observed between WDR5 and
histone H3. Residues in the protein that engage in van der Waals
contacts, hydrogen bonds or salt bridge interactions with
histone H3 are shown. Hydrogen bonds and salt bridge
interactions are delineated by orange dashed lines. (c)
Superimposition of the histone H3–binding cleft of apo-WDR5
(green) and the WDR5–histone H3 complex (blue), showing
structural rearrangements that occur upon histone binding.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2006,
13,
698-703)
copyright 2006.
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