Structural characterization of the cysteine-rich domain of TFIIH p44 subunit

In an effort to understand the structure function relationship of TFIIH, a transcription/repair factor, we focused our attention on the p44 subunit, w hich plays a central role in both mechanisms. The amino-terminal portion of p44 has been shown to be involved in the regulation of the XPD helicase ac tivity; here we show that its carboxyl-terminal domain is essential for TFI IH transcription activity and that it binds three zinc atoms through two in dependent modules. The first contains a C4 zinc finger motif, whereas the s econd is characterized by a CX(2)CX(2-4)FCADCD motif, corresponding to inte rleaved zinc binding sites. The solution structure of this second module re veals an unexpected homology with the regulatory domain of protein kinase C and provides a framework to study its role at the molecular level.