An extended winged helix domain in general transcription factor E/IIEα

Initiation of eukaryotic mRNA transcription requires melting of promoter DNA with the help of the general transcription factors TFIIE and TFIIH. Here we define a conserved and functionally essential N-terminal domain in TFE, the archaeal homolog of the large TFIIE subunit alpha. X-ray crystallography shows that this TFE domain adopts a winged helix-turn-helix (winged helix) fold, extended by specific alpha-helices at the N and C termini. Although the winged helix fold is often found in DNA-binding proteins, we show that TFE is not a typical DNA-binding winged helix protein, because its putative DNA-binding face shows a negatively charged groove and an unusually long wing, and because the domain lacks DNA-binding activity in vitro. The groove and a conserved hydrophobic surface patch on the additional N-terminal alpha-helix may, however, allow for interactions with other general transcription factors and RNA polymerase. Homology modeling shows that the TFE domain is conserved in TFIIEalpha, including the potential functional surfaces.