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PDBsum entry 2pp4
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Transcription
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PDB id
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2pp4
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References listed in PDB file
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Key reference
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Title
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A taf4-Homology domain from the corepressor eto is a docking platform for positive and negative regulators of transcription.
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Authors
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Y.Wei,
S.Liu,
J.Lausen,
C.Woodrell,
S.Cho,
N.Biris,
N.Kobayashi,
Y.Wei,
S.Yokoyama,
M.H.Werner.
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Ref.
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Nat Struct Biol, 2007,
14,
653-661.
[DOI no: ]
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PubMed id
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Abstract
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The eight twenty-one protein, ETO, is implicated in 12%-15% of acute human
leukemias as part of a gene fusion with RUNX1 (also called AML1). Of the four
ETO domains related to Drosophila melanogaster Nervy, only two are required to
induce spontaneous myeloid leukemia upon transplantation into the mouse. One of
these domains is related in sequence to TAF4, a component of TFIID. The
structure of this domain, ETO-TAFH, is similar to yeast Rpb4 and to Escherichia
coli sigma(70); it is the first TAF-related protein with structural similarity
to the multisubunit RNA polymerases. Overlapping surfaces of ETO-TAFH interact
with an autonomous repression domain of the nuclear receptor corepressor N-CoR
and with a conserved activation domain from the E-box family of transcription
factors. Thus, ETO-TAFH acts as a structural platform that can interchange
negative and positive coregulatory proteins to control transcription.
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Figure 2.
(a) Stereo superposition of the family of 20 ETO-TAFH
structures. The structure is composed of five  helices,
H1–H5. The longest helix, H4, is kinked by 30° owing to
the presence of Pro190 in the middle of the helix. (b)
Cylindrical representation of ETO-TAFH in the same orientation
as in a, indicating the positions of the five helices.
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Figure 6.
(a) Cluster analysis of the N-CoR-R1 complex with ETO-TAFH.
Two clusters are seen, with the lowest-energy cluster circled,
representing  75%
of the 200 water-refined structures from HADDOCK (see Methods).
(b) Stereo view of representative model from the lowest-energy
cluster in a. Black band, Leu387 of N-CoR-R1. Light shading,
positions of mutations in ETO-TAFH that disrupt interaction with
N-CoR-R1 or HEB-AD1, as discussed in the text.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2007,
14,
653-661)
copyright 2007.
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