STRUCTURE OF IRF-1 WITH BOUND DNA REVEALS DETERMINANTS OF INTERFERON REGULATION

The family of interferon regulatory factor (IRF) transcription factors is important in the regulation of interferons in response to infectio n by virus and in the regulation of interferon-inducible genes(1,2). T he IRF family is characterized by a unique 'tryptophan cluster' DNA-bi nding 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(1). The structure provides the firs t three-dimensional view of a member of the growing IRF family, reveal ing a new helix-turn-helix motif that latches onto DNA through three o f the five conserved tryptophans. The moth selects a short GAAA core s equence through an obliquely angled recognition helix, with an accompa nying bending of the DNA axis in the direction of the protein. Togethe r, these features suggest a basis for the occurrence of GAAA repeats w ithin IRF response elements and provide clues to the assembly of the h igher-order interferon-beta enhancesome.