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PDBsum entry 2gf7
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Metal binding protein
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PDB id
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2gf7
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References listed in PDB file
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Key reference
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Title
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Recognition of histone h3 lysine-4 methylation by the double tudor domain of jmjd2a.
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Authors
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Y.Huang,
J.Fang,
M.T.Bedford,
Y.Zhang,
R.M.Xu.
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Ref.
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Science, 2006,
312,
748-751.
[DOI no: ]
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PubMed id
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Abstract
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Biological responses to histone methylation critically depend on the faithful
readout and transduction of the methyl-lysine signal by "effector" proteins, yet
our understanding of methyl-lysine recognition has so far been limited to the
study of histone binding by chromodomain and WD40-repeat proteins. The double
tudor domain of JMJD2A, a Jmjc domain-containing histone demethylase, binds
methylated histone H3-K4 and H4-K20. We found that the double tudor domain has
an interdigitated structure, and the unusual fold is required for its ability to
bind methylated histone tails. The cocrystal structure of the JMJD2A double
tudor domain with a trimethylated H3-K4 peptide reveals that the trimethyl-K4 is
bound in a cage of three aromatic residues, two of which are from the tudor-2
motif, whereas the binding specificity is determined by side-chain interactions
involving amino acids from the tudor-1 motif. Our study provides mechanistic
insights into recognition of methylated histone tails by tudor domains and
reveals the structural intricacy of methyl-lysine recognition by two closely
spaced effector domains.
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Figure 1.
Fig. 1. JMJD2A structure. (A) A schematic drawing of the domain
structure of JMJD2A. (B) Alignment of the double tudor domain
sequences of three human JMJD2 homologs, one from zebrafish
(Ensemble ID: DARP00000024692) and another from frog (Ensemble
ID: XETP00000001152), and human 53BP1. Secondary-structure
elements (orange and green for the first and second tudor
motifs, respectively), their nomenclature, and the amino acid
numbering of JMJD2A are shown above the sequences. The
secondary-structure elements of the 53BP1 double tudor domain
are delineated below the sequences. JMJD2A residues subjected to
mutational studies are indicated by stars. (C) The structure of
the JMJD2A double tudor domain (ribbon representation) in
complex with a trimethylated H3K4 peptide (ball-and-stick
model). Regions spanning the first and second tudor motifs are
colored orange and green, respectively. The dotted line
indicates a segment of seven disordered residues. (D) The
structure of the double tudor domain of 53BP1 shown in a ribbon
representation. Secondary-structure elements in (C) and (D) are
colored as in (B).
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Figure 2.
Fig. 2. JMJD2A double tudor domain-H3K4Me3 peptide
interactions. (A) The double tudor domain as seen in a surface
representation with electrostatic potential distribution colored
red for negatively charged, white for neutral, and blue for
positively charged areas. The peptide is shown as a stick model
superimposed with the surrounding 2F[o] - F[c] electron density
map (displayed at 1.2  contour level).
(B) A stereo view of the methyl-H3K4 (colored cyan)
bindingaromaticcagesuperimposedwiththe methyllysine binding
aromatic cage of the chromo domain of HP1 (gray). Tudor-1 and
Tudor-2 residues are colored orange and green, respectively. (C)
A detailed view of JMJD2A-H3K4Me3 interactions. The peptide and
the HTD-2 residues involved are shown in a stick model. Dashed
lines indicate hydrogen bonds. The same coloring scheme as in
Fig. 1 is used.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2006,
312,
748-751)
copyright 2006.
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