title: Crystal structure of the Bach1 BTB domain and its regulation of homodimerization.
abstract: The BTB/POZ domain is known as a protein-protein interaction motif that mediates homodimer and higher order self-associations. Proteins containing the BTB domain exist throughout eukaryotes; however, there is little information about the mechanism that determines the oligomeric state of the BTB domain. To address this question, we have determined the X-ray structure of the mouse Bach1 BTB domain. The present structure is similar to the previously determined BTB domain folds, including the human Bach1 BTB domain; however, distinct structural features are present, such as a novel homodimer interaction surface. The homodimer formation was found to involve a novel hydrogen bond network and interactions between hydrophobic surfaces of the kinked N-terminus (N-hook) and the partner's C-terminal residues. The deletion of the N-hook resulted in the conversion of the homodimer into a monomer in solution, indicating that the N-hook promotes the homodimerization of the mBach1 BTB domain. We have also found that the BTB domain of Bach2, a protein highly related to Bach1, is present as a monomer due to a short peptide insertion at the N-hook. These results represent the first example of the key modulatory element of BTB domain homodimerization.
authors.affiliation: Biomedical Engineering Research Organization, Tohoku University, Aoba-ku, Sendai, Japan.
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Ito
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe-Matsui
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Murayama
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D025941:Protein Interaction Mapping; D055503:Protein Multimerization / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D017386:Sequence Homology, Amino Acid
chemical_list: C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors