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PDBsum entry 4om2
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Transcription, DNA binding
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PDB id
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4om2
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References listed in PDB file
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Key reference
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Title
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Molecular functions of the tle tetramerization domain in wnt target gene repression.
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Authors
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J.V.Chodaparambil,
K.T.Pate,
M.R.Hepler,
B.P.Tsai,
U.M.Muthurajan,
K.Luger,
M.L.Waterman,
W.I.Weis.
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Ref.
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Embo J, 2014,
33,
719-731.
[DOI no: ]
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PubMed id
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Abstract
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Wnt signaling activates target genes by promoting association of the
co-activator β-catenin with TCF/LEF transcription factors. In the absence of
β-catenin, target genes are silenced by TCF-mediated recruitment of TLE/Groucho
proteins, but the molecular basis for TLE/TCF-dependent repression is unclear.
We describe the unusual three-dimensional structure of the N-terminal Q domain
of TLE1 that mediates tetramerization and binds to TCFs. We find that
differences in repression potential of TCF/LEFs correlates with their affinities
for TLE-Q, rather than direct competition between β-catenin and TLE for TCFs as
part of an activation-repression switch. Structure-based mutation of the TLE
tetramer interface shows that dimers cannot mediate repression, even though they
bind to TCFs with the same affinity as tetramers. Furthermore, the TLE Q
tetramer, not the dimer, binds to chromatin, specifically to K20 methylated
histone H4 tails, suggesting that the TCF/TLE tetramer complex promotes
structural transitions of chromatin to mediate repression.
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