CRYSTAL-STRUCTURE OF THE BTB DOMAIN FROM PLZF

The BTB domain (also known as the POZ domain) is an evolutionarily con served protein-protein interaction motif found at the N terminus of 5- 10% of C2H2-type zinc-finger transcription factors, as well as in some actin-associated proteins bearing the kelch motif. Many BTB proteins are transcriptional regulators that mediate gene expression through th e control of chromatin conformation. In the human promyelocytic leukem ia zinc finger (PLZF) protein, the BTB domain has transcriptional repr ession activity, directs the protein to a nuclear punctate pattern, an d interacts with components of the histone deacetylase complex. The as sociation of the PLZF BTB domain with the histone deacetylase complex provides a mechanism of linking the transcription factor with enzymati c activities that regulate chromatin conformation. The crystal structu re of the BTB domain of PLZF was determined at 1.9 Angstrom resolution and reveals a tightly intertwined dimer with an extensive hydrophobic interface. Approximately one-quarter of the monomer surface area is i nvolved in the dimer intermolecular contact. These features are typica l of obligate homodimers, and we expect the full-length PLZF protein t o exist as a branched transcription factor with two C-terminal DNA-bin ding regions. A surface-exposed groove lined with conserved amino acid s is formed at the dimer interface, suggestive of a peptide-binding si te. This groove may represent the site of interaction of the PLZF BTB domain with nuclear corepressors or other nuclear proteins.