Novel zinc finger motif in the basal transcriptional machinery : three-dimensional NMR studies of the nucleic acid binding domain of transcriptional elongation factor TFIIS

Abstract

Transcriptional elongation provides a key control point in the regulation of eukaryotic gene

expression. Here we describe homonuclear and lSN-heteronuclear 3D NMR studies of the nucleic acid

binding domain of human transcriptional elongation factor TFIIS. This domain contains a Cys4 ZnZ+-

binding site with no homology to previously characterized Cys4, Cysa, or Cysz-His2 Zn fingers. Complete

lH and I5N NMR resonance assignment of a 50-residue TFIIS peptideZnz+ complex is obtained. Its

solution structure, as determined by distance geometry/simulated annealing (DG/SA) calculations, exhibits

a novel three-stranded antiparallel p-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 three-dimensional model of the TFIIE Cys4 domain is obtained by DG-based

homology modeling. The role of the TFIIS Zn ribbon in the control of eukaryotic transcriptional elongation

is discussed.