NOVEL ZINC-FINGER MOTIF IN THE BASAL TRANSCRIPTIONAL MACHINERY - 3-DIMENSIONAL NMR-STUDIES OF THE NUCLEIC-ACID BINDING DOMAIN OF TRANSCRIPTIONAL ELONGATION-FACTOR TFIIS

Transcriptional elongation provides a key control point in the regulat ion of eukaryotic gene expression. Here we describe homonuclear and N- 15-heteronuclear 3D NMR studies of the nucleic acid binding domain of human transcriptional elongation factor TFIIS. This domain contains a Cys4 Zn2+-binding site with no homology to previously characterized Cy s4, Cys6, or Cys2-HiS2 Zn fingers. Complete H-1 and N-15 NMR resonance assignment of a 50-residue TFIIS peptide-Zn2+ complex is obtained. It s solution structure, as determined by distance geometry/simulated ann ealing (DG/SA) calculations, exhibits a novel three-stranded antiparal lel, beta-sheet (designated the Zn ribbon). Analogous sequence motifs occur in a wide class of proteins involved in RNA or DNA transactions, including human basal transcriptional initiation factor TFIIE. A thre e-dimensional model of the TFIIE Cys4 domain is obtained by DG-based h omology modeling. The role of the TFIIS Zn ribbon in the control of eu karyotic transcriptional elongation is discussed.