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PDBsum entry 1eqf
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Transcription
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PDB id
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1eqf
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure and function of a human tafii250 double bromodomain module.
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Authors
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R.H.Jacobson,
A.G.Ladurner,
D.S.King,
R.Tjian.
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Ref.
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Science, 2000,
288,
1422-1425.
[DOI no: ]
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PubMed id
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Abstract
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TFIID is a large multiprotein complex that initiates assembly of the
transcription machinery. It is unclear how TFIID recognizes promoters in vivo
when templates are nucleosome-bound. Here, it is shown that TAFII250, the
largest subunit of TFIID, contains two tandem bromodomain modules that bind
selectively to multiply acetylated histone H4 peptides. The 2.1 angstrom crystal
structure of the double bromodomain reveals two side-by-side, four-helix bundles
with a highly polarized surface charge distribution. Each bundle contains an
Nepsilon-acetyllysine binding pocket at its center, which results in a structure
ideally suited for recognition of diacetylated histone H4 tails. Thus, TFIID may
be targeted to specific chromatin-bound promoters and may play a role in
chromatin recognition.
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Figure 3.
Fig. 3. Electrostatic charge distribution and binding pockets.
Delphi electrostatic potential calculated and mapped onto the
Connelly solvent accessible surface using InsightII calculated
with coordinates corresponding to the core domain (residues 1379
to 1625). Simulated ionic strength was set to 0.145 M with a
bulk solvent dielectric constant of 80. The first seven
NH[2]-terminal residues from a symmetry-equivalent molecule are
shown as a green stick model. The first three residues (1359 to
1361) are visible binding into the putative acetyllysine
recognition pocket of the first domain. (A) Orientation of the
hTAF[II]250-DBD is the same as that of Fig. 2. Numerous
clustered lysine and arginine residues result in an extended
basic surface. (B) Reverse side of the double bromodomain
relative to (A) displaying the acidic stripe present running
across the top of the molecule. (C) Putative binding surface of
the double bromodomain viewed from the bottom surface of (A).
Two deep pits (labeled) at the center of each four-helix bundle
are readily apparent and are separated by about 25 Å.
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Figure 4.
Fig. 4. Simplified model for assembly of transcription
complexes on chromatin-bound templates. First, recruitment of a
HAT-containing coactivator complex via interactions with an
upstream DNA binding protein occurs. After recruitment, the
coactivator HAT activity might acetylate the NH[2]-terminal
histone tails (light blue tails) of nearby nucleosomes (upper).
Acetylated histone tails positioned at an appropriate distance
from the start site of a gene might then help to recruit TFIID
by interactions with the TAF[II]250 bromodomains. Nonspecific
interactions between the TAF[II]250 bromodomains and the
promoter DNA as well as other TAF-DNA interactions could further
increase affinity of TFIID for the core promoter. The
bromodomain-mediated increase in affinity for the acetylated
histones near the core promoter would provide a linkage between
histone acetylation and transcriptional activation by enhanced
preinitiation complex formation. Such a model would not preclude
other activation pathways.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2000,
288,
1422-1425)
copyright 2000.
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