Crystal structure of PU.1/IRF-4/DNA ternary complex.

The Ets and IRF transcription factor families contain structurally divergent members, PU.1, Spi-B and IRF-4 (Pip), IRF-8 (ICSBP), respectively, which have evolved to cooperatively assemble on composite DNA elements and regulate gene expression in the immune system. Whereas PU.1 recruits IRF-4 or IRF-8 to DNA, it exhibits an anticooperative interaction with IRF-1 and IRF-2. We report here the structure of the ternary complex formed with the DNA binding domains of PU.1 and IRF-4 on a composite DNA element. The DNA in the complex contorts into an unusual S shape that juxtaposes PU.1 and IRF-4 for selective electrostatic and hydrophobic interactions across the central minor groove. Together, the protein-protein and protein-DNA interactions provide insights into the stereochemical basis of cooperativity and anti-cooperativity between Ets and IRF factors.