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PDBsum entry 2k8f
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Transferase/transcription
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PDB id
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2k8f
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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 p300 taz2-P53 tad1 binding and modulation by phosphorylation.
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Authors
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H.Feng,
L.M.Jenkins,
S.R.Durell,
R.Hayashi,
S.J.Mazur,
S.Cherry,
J.E.Tropea,
M.Miller,
A.Wlodawer,
E.Appella,
Y.Bai.
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Ref.
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Structure, 2009,
17,
202-210.
[DOI no: ]
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PubMed id
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Abstract
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Coactivators CREB-binding protein and p300 play important roles in mediating the
transcriptional activity of p53. Until now, however, no detailed structural
information has been available on how any of the domains of p300 interact with
p53. Here, we report the NMR structure of the complex of the Taz2 (C/H3) domain
of p300 and the N-terminal transactivation domain of p53. In the complex, p53
forms a short alpha helix and interacts with the Taz2 domain through an extended
surface. Mutational analyses demonstrate the importance of hydrophobic residues
for complex stabilization. Additionally, they suggest that the increased
affinity of Taz2 for p53(1-39) phosphorylated at Thr(18) is due in part to
electrostatic interactions of the phosphate with neighboring arginine residues
in Taz2. Thermodynamic experiments revealed the importance of hydrophobic
interactions in the complex of Taz2 with p53 phosphorylated at Ser(15) and
Thr(18).
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Figure 1.
Figure 1. Structure of the Taz2-p53[2–39] Complex
(A)
Stereo image of the overlay of ten lowest-energy NMR structures
of the complex between p53[15–27] (magenta) and the Taz2
domain of p300 (gray). The structures are superimposed on the
Cα traces.
(B) Plot of backbone amide ^15N-{^1H}
heteronuclear NOEs of p53[2–39].
(C) Cylinder model of
the average conformation of the complex. p53 is shown in magenta
and the helices of Taz2 are shown in blue (α1), lilac (α2),
orange (α3), and red (α4). Zinc ions in Taz2, modeled as green
spheres, were added according to zinc-coordination distances
into the known binding cage.
(D) Secondary chemical shift
difference of p53[2-39] in the complex (measured Cα chemical
shift − random coil value).
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Figure 2.
Figure 2. Stabilizing Interactions between p53[2–39] and
Taz2
(A) Model of the Taz2-p53[2–39] complex, showing
residues that make hydrophobic contacts. Contacting residues are
labeled in white for Taz2 (gray surface representation) and red
for p53[2–39] (blue ribbon).
(B) Model of the
Taz2-p53[2–39] complex, colored by electrostatic potential
(red represents negative, blue indicates positive). Taz2 is
shown in a solid representation, and p53[2–39] as a mesh.
(C) Model of the Taz2-p53[2–39] complex, showing residues that
make electrostatic contacts. Contacting residues are labeled in
white for Taz2 (gray surface representation) and red for
p53[2–39] (blue ribbon).
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2009,
17,
202-210)
copyright 2009.
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