Structure of IRF-1 with bound DNA reveals determinants of interferon regulation

Nature. 1998 Jan 1;391(6662):103-6. doi: 10.1038/34224.


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.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Helix-Loop-Helix Motifs
  • Interferon Regulatory Factor-1
  • Interferon-beta / genetics*
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Phosphoproteins / chemistry*
  • Phosphoproteins / metabolism
  • Promoter Regions, Genetic
  • Protein Conformation


  • DNA-Binding Proteins
  • Interferon Regulatory Factor-1
  • Phosphoproteins
  • Interferon-beta
  • DNA

Associated data

  • PDB/1IF1
  • SWISSPROT/Q13568
  • SWISSPROT/Q92985