Abstract
The transcriptional corepressors BCOR, SMRT, and NCoR are known to bind competitively to the BCL6 BTB domain despite the fact that BCOR has no detectable sequence similarity to the other two corepressors. We have identified a 17 residue motif from BCOR that binds directly to the BCL6 BTB domain and determined the crystal structure of the complex to a resolution of 2.6 A. Remarkably, the BCOR BCL6 binding domain (BCOR(BBD)) peptide binds in the same BCL6 binding site as the SMRT(BBD) peptide despite the lack of any significant sequence similarity between the two peptides. Mutations of critical BCOR(BBD) residues cause the disruption of the BCL6 corepression activities of BCOR, and a BCOR(BBD) peptide blocks BCL6-mediated transcriptional repression and kills lymphoma cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Binding Sites
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Crystallography, X-Ray
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Dimerization
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Histidine / chemistry
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Models, Chemical
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Peptides / isolation & purification
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Peptides / metabolism*
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Protein Binding
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Proto-Oncogene Proteins / chemistry*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-6 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-6 / chemistry*
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Proto-Oncogene Proteins c-bcl-6 / isolation & purification
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Proto-Oncogene Proteins c-bcl-6 / metabolism*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / chemistry*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Sequence Alignment
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Thioredoxins / metabolism
Substances
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BCOR protein, human
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Peptides
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-6
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Recombinant Fusion Proteins
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Repressor Proteins
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Histidine
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Thioredoxins