Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain.
BCL6 encodes a transcription factor that represses genes necessary for the terminal differentiation of lymphocytes within germinal centers, and the misregulated expression of this factor is strongly implicated in several types of B cell lymphoma. The homodimeric BTB domain of BCL6 (also known as the POZ domain) is required for the repression activity of the protein and interacts directly with the SMRT and N-CoR corepressors that are found within large multiprotein histone deacetylase-containing complexes. We have identified a 17 residue fragment from SMRT that binds to the BCL6 BTB domain, and determined the crystal structure of the complex to 2.2 A. Two SMRT fragments bind symmetrically to the BCL6 BTB homodimer and, in combination with biochemical and in vivo data, the structure provides insight into the basis of transcriptional repression by this critical B cell lymphoma protein.
Ahmad
K Farid
KF
Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
Melnick
Ari
A
Lax
Stuart
S
Bouchard
Denis
D
Liu
Jun
J
Kiang
Chih-Li
CL
Mayer
Sebastian
S
Takahashi
Shinichiro
S
Licht
Jonathan D
JD
Privé
Gilbert G
GG
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D046912:Multiprotein Complexes; D056985:Nuclear Receptor Co-Repressor 2; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors