title: Structure of IRF-1 with bound DNA reveals determinants of interferon regulation.
abstract: The family of interferon regulatory factor (IRF) transcription factors is important in the regulation of interferons in response to infection by virus and in the regulation of interferon-inducible genes. The IRF family is characterized by a unique 'tryptophan cluster' DNA-binding region. Here we report the crystal structure of the IRF-1 region bound to the natural positive regulatory domain I (PRD I) DNA element from the interferon-beta promoter. The structure provides the first three-dimensional view of a member of the growing IRF family, revealing a new helix-turn-helix motif that latches onto DNA through three of the five conserved tryptophans. The motif selects a short GAAA core sequence through an obliquely angled recognition helix, with an accompanying bending of the DNA axis in the direction of the protein. Together, these features suggest a basis for the occurrence of GAAA repeats within IRF response elements and provide clues to the assembly of the higher-order interferon-beta enhancesome.
authors.affiliation: Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Escalante
authors.forename: J
authors.initials: J
authors.lastname: Yie
authors.forename: D
authors.initials: D
authors.lastname: Thanos
authors.forename: A K
authors.initials: AK
authors.lastname: Aggarwal
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D050856:Interferon Regulatory Factor-1; D016899:Interferon-beta / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation
chemical_list: D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D016899:Interferon-beta; D004247:DNA