title: Solution structure of the IRF-2 DNA-binding domain: a novel subgroup of the winged helix-turn-helix family.
abstract: BACKGROUND
  The transcription of interferon (IFN) and IFN-inducible genes is mainly regulated by the interferon regulatory factor (IRF) family of proteins, which recognize a unique AAGTGA hexamer repeat motif in the regulatory region of IFN genes. A DNA-binding domain of approximately 100 amino acids has been commonly found in the IRF family of proteins, but it has no sequence homology to known DNA-binding motifs. Elucidation of the structures of members of the IRF family is therefore useful to the understanding of the regulation and evolution of the immune system at the structural level.
  
  
  RESULTS
  The solution structure of the DNA-binding domain of interferon regulatory factor-2 (IRF-2) has been determined by NMR spectroscopy. It is composed of a four-stranded antiparallel beta sheet and three alpha helices, and its global fold is similar to those of the winged helix-turn-helix (wHTH) family of proteins. A long loop (Pro37-Asp51) is found immediately before the HTH motif, which is not found in other wHTH proteins. The NMR signals of residues in this long loop, as well as the second helix of the HTH motif, are strongly affected upon the addition of the hexamer repeat DNA, suggesting that these structural elements participate in DNA recognition and binding.
  
  
  CONCLUSIONS
  The structural similarity of the DNA-binding domain of IRF-2 with those of proteins in the wHTH family shows that the IRF proteins belong to the wHTH family, even though there is no apparent sequence homology among proteins of the two families. The sequential structure alignment program (SSAP) shows that IRF-2 has a slightly different structure from typical wHTH proteins, mainly in the orientation of helix 2. The IRF family of proteins should therefore be categorized into a subfamily of the wHTH family. The evidence here implies that the evolutional pathway of the IRF family is distinct from that of the other wHTH proteins, in other words, the immune system diverged from an evolutional stem at an early stage.
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Osaka, 565, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Furui
authors.forename: K
authors.initials: K
authors.lastname: Uegaki
authors.forename: T
authors.initials: T
authors.lastname: Yamazaki
authors.forename: M
authors.initials: M
authors.lastname: Shirakawa
authors.forename: M B
authors.initials: MB
authors.lastname: Swindells
authors.forename: H
authors.initials: H
authors.lastname: Harada
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Kyogoku
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry*; D019143:Evolution, Molecular; D019077:Helix-Turn-Helix Motifs / Q000502:physiology*; D050836:Interferon Regulatory Factor-2; D016899:Interferon-beta / Q000737:chemistry; D007716:Kluyveromyces / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D012097:Repressor Proteins; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D050836:Interferon Regulatory Factor-2; C494230:Irf2 protein, mouse; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D016899:Interferon-beta; D004247:DNA