TitleStructure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer.
Publication TypeJournal Article
Year of Publication2008
AuthorsGhetu, Alexandru F., Corcoran Connie M., Cerchietti Leandro, Bardwell Vivian J., Melnick Ari, and Prive Gilbert G.
JournalMol Cell
Volume29
Issue3
Pagination384-91
Date Published2008 Feb 15
ISSN1097-2765
KeywordsAmino Acid Motifs, Amino Acid Sequence, Binding Sites, Crystallography, X-Ray, Dimerization, Histidine, Models, Chemical, Models, Molecular, Molecular Sequence Data, Mutation, Peptides, Protein Binding, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-6, Recombinant Fusion Proteins, Repressor Proteins, Sequence Alignment, Thioredoxins
Abstract

<p>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.</p>

DOI10.1016/j.molcel.2007.12.026
Alternate JournalMol Cell
PubMed ID18280243
PubMed Central IDPMC2665293
Grant ListR01 CA071540 / CA / NCI NIH HHS / United States
R01 CA104348 / CA / NCI NIH HHS / United States
R01 CA104348-05 / CA / NCI NIH HHS / United States
R01 CA71540 / CA / NCI NIH HHS / United States