An Extended Winged Helix Domain in General Transcription Factor E/IIE&alpha

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 TFIIE{alpha}, including the potential functional surface