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

doi:10.1016/j.molcel.2007.12.026

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

Genetics, Cell Biology and Development (TMED)

Research output: Contribution to journal › Article › peer-review

126 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 (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.

Original language	English (US)
Pages (from-to)	384-391
Number of pages	8
Journal	Molecular Cell
Volume	29
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2007.12.026
State	Published - 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

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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 {\AA}. 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.",

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

Abstract

Bibliographical note

Keywords

UN SDGs

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