Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences

There has been growing interest in the role of the IRF (interferon regulato ry factor) family of transcription factors in the regulation of immune resp onses, cytokine signaling, and oncogenesis. These members are characterized by their well-conserved DNA binding domains at the N-terminal regions, Her e we report the 2.2 Angstrom resolution crystal structure of the DNA bindin g domain of one such family member, IRF-2, bound to DNA. The structure reve als its recognition sequence, AANNGAAA (here, recognized bases are underlin ed and in bold, and N indicates any base), and its cooperative binding to a tandem repeat of the GAAA core sequence induced by DNA structure distortio ns, These facts explain well the diverse binding properties of the IRF fami ly members, which bind to both single and tandemly repeated sequences. Furt hermore, we also identified the 'helix-hairpin-strand motif' at the C termi nus of the recognition helix as a metal binding site that is commonly found in certain classes of DNA-interactive proteins, Our results provide new in sights into the structure and function of this family of transcription fact ors.