title: Insights into strand exchange in BTB domain dimers from the crystal structures of FAZF and Miz1.
abstract: The BTB domain is a widely distributed protein-protein interaction motif that is often found at the N-terminus of zinc finger transcription factors. Previous crystal structures of BTB domains have revealed tightly interwound homodimers, with the N-terminus from one chain forming a two-stranded anti-parallel beta-sheet with a strand from the other chain. We have solved the crystal structures of the BTB domains from Fanconi anemia zinc finger (FAZF) and Miz1 (Myc-interacting zinc finger 1) to resolutions of 2.0 A and 2.6 A, respectively. Unlike previous examples of BTB domain structures, the FAZF BTB domain is a nonswapped dimer, with each N-terminal beta-strand associated with its own chain. As a result, the dimerization interface in the FAZF BTB domain is about half as large as in the domain-swapped dimers. The Miz1 BTB domain resembles a typical swapped BTB dimer, although it has a shorter N-terminus that is not able to form the interchain sheet. Using cysteine cross-linking, we confirmed that the promyelocytic leukemia zinc finger (PLZF) BTB dimer is strand exchanged in solution, while the FAZF BTB dimer is not. A phylogenic tree of the BTB fold based on both sequence and structural features shows that the common ancestor of the BTB domain in BTB-ZF (bric à brac, tramtrack, broad-complex zinc finger) proteins was a domain-swapped dimer. The differences in the N-termini seen in the FAZF and Miz1 BTB domains appear to be more recent developments in the structural evolution of the domain.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stogios
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Cuesta-Seijo
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Neil C
authors.initials: NC
authors.lastname: Pomroy
authors.forename: Gilbert G
authors.initials: GG
authors.lastname: Privé
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012097:Repressor Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
chemical_list: D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; C107961:ZBTB17 protein, human; C498646:ZBTB32 protein, human