STRUCTURE OF A NEW NUCLEIC-ACID-BINDING MOTIF IN EUKARYOTIC TRANSCRIPTIONAL ELONGATION-FACTOR TFIIS

TRANSCRIPTIONAL elongation involves dynamic interactions among RNA pol ymerase and single-stranded and double-stranded nucleic acids in the t ernary complex1-4. In prokaryotes its regulation provides an important mechanism of genetic control1. Analogous eukaryotic mechanisms are no t well understood5, but may control expression of proto-oncogenes6,7 a nd viruses, including the human immunodeficiency virus HIV-1 (ref. 8). The highly conserved eukaryotic transcriptional elongation factor TFI IS9 enables RNA polymerase II (RNAPII) to read though pause or termina tion sites, nucleosomes and sequence-specific DNA-binding proteins10-1 4 . Two distinct domains of human TFIIS, which bind RNAPII and nucleic acids, regulate read-through10 and possibly nascent transcript cleava ge11-15. Here we describe the three-dimensional NMR16 structure of a C ys4 nucleic-acid-binding domain from human TFIIS9,10. Unlike previousl y characterized zinc modules17-21, which contain an alpha-helix, this structure consists of a three-stranded beta-sheet. Analogous Cys4, str uctural motifs may occur in other proteins involved in DNA or RNA tran sactions22-24, including RNAPII itself25. This new structure, designat ed the Zn ribbon, extends the repertoire of Zn-mediated peptide archit ectures26 and highlights the growing recognition of the beta-sheet as a motif of nucleic-acid recognition27,28.