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PDBsum entry 1cs3
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Transcription
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PDB id
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1cs3
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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-Function studies of the btb/poz transcriptional repression domain from the promyelocytic leukemia zinc finger oncoprotein.
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Authors
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X.Li,
H.Peng,
D.C.Schultz,
J.M.Lopez-Guisa,
F.J.Rauscher,
R.Marmorstein.
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Ref.
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Cancer Res, 1999,
59,
5275-5282.
[Ref: ]
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PubMed id
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Abstract
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The evolutionarily conserved BTB/POZ domain from the promyelocytic leukemia zinc
finger (PLZF) oncoprotein mediates transcriptional repression through the
recruitment of corepressor proteins containing histone deacetylases in acute
promyelocytic leukemia. We have determined the 2.0 A crystal structure of the
BTB/POZ domain from PLZF (PLZF-BTB/POZ), and have carried out biochemical
analysis of PLZF-BTB/POZ harboring site-directed mutations to probe
structure-function relationships. The structure reveals a novel alpha/beta
homodimeric fold in which dimer interactions occur along two surfaces of the
protein subunits. The conservation of BTB/POZ domain residues at the core of the
protomers and at the dimer interface implies an analogous fold and dimerization
mode for BTB/POZ domains from otherwise functionally unrelated proteins.
Unexpectedly, the BTB/POZ domain forms dimer-dimer interactions in the crystals,
suggesting a mode for higher-order protein oligomerization for BTB/POZ-mediated
transcriptional repression. Biochemical characterization of PLZF-BTB/POZ
harboring mutations in conserved residues involved in protein dimerization
reveals that the integrity of the dimer interface is exquisitely sensitive to
mutation and that dimer formation is required for wild-type levels of
transcriptional repression. Interestingly, similar mutational analysis of
residues within a pronounced protein cleft along the dimer interface, which had
been implicated previously for interaction with corepressors, has negligible
effects on dimerization or transcriptional repression. Together, these studies
form a structure-function framework for understanding BTB/POZ-mediated
oligomerization and transcriptional repression properties.
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