Crystal structure of the BTB domain from the LRF/ZBTB7 transcriptional regulator.
BTB-zinc finger (BTB-ZF) proteins are transcription regulators with roles in development, differentiation, and oncogenesis. In these proteins, the BTB domain (also known as the POZ domain) is a protein-protein interaction motif that contains a dimerization interface, a possible oligomerization surface, and surfaces for interactions with other factors, including nuclear co-repressors and histone deacetylases. The BTB-ZF protein LRF (also known as ZBTB7, FBI-1, OCZF, and Pokemon) is a master regulator of oncogenesis, and represses the transcription of a variety of important genes, including the ARF, c-fos, and c-myc oncogenes and extracellular matrix genes. We determined the crystal structure of the BTB domain from human LRF to 2.1 A and observed the canonical BTB homodimer fold. However, novel features are apparent on the surface of the homodimer, including differences in the lateral groove and charged pocket regions. The residues that line the lateral groove have little similarity with the equivalent residues from the BCL6 BTB domain, and we show that the 17-residue BCL6 Binding Domain (BBD) from the SMRT co-repressor does not bind to the LRF BTB domain.
Stogios
Peter J
PJ
Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, Ontario, Canada.
Chen
Lu
L
Privé
Gilbert G
GG
D000595:Amino Acid Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C485514:ZBTB7A protein, human