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PDBsum entry 2rnw
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Transferase/nuclear protein
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PDB id
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2rnw
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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 of site-Specific histone recognition by the bromodomains of human coactivators pcaf and cbp/p300.
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Authors
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L.Zeng,
Q.Zhang,
G.Gerona-Navarro,
N.Moshkina,
M.M.Zhou.
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Ref.
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Structure, 2008,
16,
643-652.
[DOI no: ]
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PubMed id
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Abstract
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Histone lysine acetylation is central to epigenetic control of gene
transcription. Bromodomains of chromosomal proteins function as acetyl-lysine
(Kac) binding domains. However, how bromodomains recognize site-specific
histones remains unanswered. Here, we report three three-dimensional solution
structures of the bromodomains of the human transcriptional coactivators
CREB-binding protein (CBP) and p300/CBP-associated factor (PCAF) bound to
peptides derived from histone acetylation sites at lysines 36 and 9 in H3, and
lysine 20 in H4. From structural and biochemical binding analyses, we determine
consensus histone recognition by the bromodomains of PCAF and CBP, which
represent two different subgroups of the bromodomain family. Through bromodomain
residues in the ZA and BC loops, PCAF prefers acetylation sites with a
hydrophobic residue at (Kac+2) position and a positively charged or aromatic
residue at (Kac+3), whereas CBP favors bulky hydrophobic residues at (Kac+1) and
(Kac+2), a positively charged residue at (Kac-1), and an aromatic residue at
(Kac-2).
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Figure 1.
Figure 1. 3D Structures of Bromodomains Bound to Acetylated
Histone Peptides
The structures of the
bromodomain/acetylated histone peptide complexes are shown in
three different illustrations: stereoview of the backbone atoms
(N, Cα, and C′) of 25 superimposed NMR structures of the
complexes (left); ribbons representation of the average
minimized NMR structure of the complexes in a similar
orientation, prepared using Pymol (middle); and surface
electrostatic potential representation of the protein with the
peptide in a ball-and-stick depiction (right).
(A–C) The
PCAF bromodomain/H3-K36ac complex.
(D–F) The PCAF
bromodomain/H3-K9ac complex.
(G–I) The CBP
bromodomain/H4-K20ac complex.
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Figure 3.
Figure 3. The Structural Basis of Histone Recognition by the
CBP Bromodomain
(A and B) Recognition of the acetyl-lysine
and its flanking residues in the H4-K20ac peptide by the human
CBP bromodomain, respectively.
(C and D) Recognition of the
acetyl-lysine and its flanking residues of the p53-K382ac
peptide by the human CBP bromodomain (PDB code: 1JSP),
respectively.
Side chains of protein or peptide residues
are color-coded by atom types in the same scheme as that in
Figure 2.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2008,
16,
643-652)
copyright 2008.
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