Transcriptional elongation involves dynamic interactions among RNA polymerase 
and single-stranded and double-stranded nucleic acids in the ternary complex. In 
prokaryotes its regulation provides an important mechanism of genetic control. 
Analogous eukaryotic mechanisms are not well understood, but may control 
expression of proto-oncogenes and viruses, including the human immunodeficiency 
virus HIV-1 (ref. 8). The highly conserved eukaryotic transcriptional elongation 
factor TFIIS enables RNA polymerase II (RNAPII) to read though pause or 
termination sites, nucleosomes and sequence-specific DNA-binding proteins. Two 
distinct domains of human TFIIS, which bind RNAPII and nucleic acids, regulate 
read-through and possibly nascent transcript cleavage. Here we describe the 
three-dimensional NMR structure of a Cys4 nucleic-acid-binding domain from human 
TFIIS. Unlike previously characterized zinc modules, which contain an 
alpha-helix, this structure consists of a three-stranded beta-sheet. Analogous 
Cys4 structural motifs may occur in other proteins involved in DNA or RNA 
transactions, including RNAPII itself. This new structure, designated the Zn 
ribbon, extends the repertoire of Zn-mediated peptide architectures and 
highlights the growing recognition of the beta-sheet as a motif of nucleic-acid 
recognition.