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PDBsum entry 2b2u
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Peptide binding protein
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PDB id
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2b2u
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References listed in PDB file
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Key reference
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Title
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Double chromodomains cooperate to recognize the methylated histone h3 tail.
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Authors
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J.F.Flanagan,
L.Z.Mi,
M.Chruszcz,
M.Cymborowski,
K.L.Clines,
Y.Kim,
W.Minor,
F.Rastinejad,
S.Khorasanizadeh.
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Ref.
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Nature, 2005,
438,
1181-1185.
[DOI no: ]
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PubMed id
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Abstract
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Chromodomains are modules implicated in the recognition of lysine-methylated
histone tails and nucleic acids. CHD (for chromo-ATPase/helicase-DNA-binding)
proteins regulate ATP-dependent nucleosome assembly and mobilization through
their conserved double chromodomains and SWI2/SNF2 helicase/ATPase domain. The
Drosophila CHD1 localizes to the interbands and puffs of the polytene
chromosomes, which are classic sites of transcriptional activity. Other CHD
isoforms (CHD3/4 or Mi-2) are important for nucleosome remodelling in histone
deacetylase complexes. Deletion of chromodomains impairs nucleosome binding and
remodelling by CHD proteins. Here we describe the structure of the tandem
arrangement of the human CHD1 chromodomains, and its interactions with histone
tails. Unlike HP1 and Polycomb proteins that use single chromodomains to bind to
their respective methylated histone H3 tails, the two chromodomains of CHD1
cooperate to interact with one methylated H3 tail. We show that the human CHD1
double chromodomains target the lysine 4-methylated histone H3 tail (H3K4me), a
hallmark of active chromatin. Methylammonium recognition involves two aromatic
residues, not the three-residue aromatic cage used by chromodomains of HP1 and
Polycomb proteins. Furthermore, unique inserts within chromodomain 1 of CHD1
block the expected site of H3 tail binding seen in HP1 and Polycomb, instead
directing H3 binding to a groove at the inter-chromodomain junction.
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Figure 3.
Figure 3: Methyllysine binding by human CHD1. a, The
bound-peptide structure of H3K4me3 (green), H3K4me1 (yellow),
H3K4me3R2me2a (cyan) and H3K4me3T3ph (red). b, The aromatic
cages from HP1 (blue) and Polycomb (cyan) with methyllysines 9
and 27. c, Fluorescence polarization peptide binding assays
using human or yeast CHD1. Using H3K4me3 peptide, human CHD1
(black) binds with a K[d] of 5  M,
W67L-human CHD1 (cyan) does not bind, W64L-human CHD1 (yellow)
binds with a K[d] of 290 M,
and budding yeast CHD1 (red) does not bind. W64L and W67L-human
CHD1 do not allow binding to H3K4me1 or the unmodified peptide.
d, Effect of adjacent peptide modifications. Black, H3K4me3;
cyan, H3K4me3R2me2a; red, H3K4me3T3ph.
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Figure 4.
Figure 4: Comparison of CHD1 with HP1 and Polycomb. a, HP1
chromodomain (blue) in complex with H3K9me3 (brown) superimposed
on CHD1 chromodomain 1 (cyan and yellow) in complex with H3K4me3
(green). b, Polycomb chromodomain (blue) in complex with
H3K27me3 (brown) superimposed on CHD1 chromodomain 1 (cyan and
yellow) in complex with H3K4me3 (green).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2005,
438,
1181-1185)
copyright 2005.
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