Structure of a BCOR Corepressor Peptide in Complex with the BCL6 BTB Domain Dimer

Alexandru F. Ghetu, Connie M. Corcoran, Leandro Cerchietti, Vivian J. Bardwell, Ari Melnick, Gilbert G. Privé

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

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 Å. Remarkably, the BCOR BCL6 binding domain (BCORBBD) peptide binds in the same BCL6 binding site as the SMRTBBD peptide despite the lack of any significant sequence similarity between the two peptides. Mutations of critical BCORBBD residues cause the disruption of the BCL6 corepression activities of BCOR, and a BCORBBD peptide blocks BCL6-mediated transcriptional repression and kills lymphoma cells.

Original languageEnglish (US)
Pages (from-to)384-391
Number of pages8
JournalMolecular Cell
Volume29
Issue number3
DOIs
StatePublished - Feb 15 2008

Bibliographical note

Funding Information:
This work is supported in part by a grant to G.G.P. from the National Cancer Institute of Canada. A.F.G. is supported by a CIHR fellowship. V.J.B. is supported by NCI R01 CA71540. A.M. is supported by NCI R01 CA104348, the Leukemia and Lymphoma Society, the Chemotherapy Foundation, and the G&P Foundation. G.G.P. and A.M. are supported by a Program Grant from the Samuel Waxman Cancer Research Foundation. L.C. is supported by a National Cancer Institute Oncology Faculty Development Award. Use of the Argonne National Laboratory Structural Biology Center beamline 19ID at the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Biological and Environmental Research, under Contract No. W-31-109-ENG-38.

Keywords

  • DNA

Fingerprint

Dive into the research topics of 'Structure of a BCOR Corepressor Peptide in Complex with the BCL6 BTB Domain Dimer'. Together they form a unique fingerprint.

Cite this