Structure of a (Cys 3 His) zinc ribbon, a ubiquitous motif in archaeal and eucaryal transcription

Abstract

Transcription factor IIB (TFIIB) is an essential component in the formation of the transcription initiation complex in eucaryal and archaeal transcription. TFIIB interacts with a promoter complex containing the TATA‐binding protein (TBP) to facilitate interaction with RNA polymerase II (RNA pol II) and the associated transcription factor IIF (TFIIF). TFIIB contains a zinc‐binding motif near the N‐terminus that is directly involved in the interaction with RNA pol II/ TFIIF and plays a crucial role in selecting the transcription initiation site. The solution structure of the N‐terminal residues 2–59 of human TFIIB was determined by multidimensional NMR spectroscopy. The structure consists of a nearly tetrahedral Zn(Cys) 3 (His) 1 site confined by type I and “rubredoxin” turns, three antiparallel β–strands, and disordered loops. The structure is similar to the reported zinc‐ribbon motifs in several transcription‐related proteins from archaea and eucarya, including Pyrococcus furiosus transcription factor B ( Pf TFB), human and yeast transcription factor IIS (TFIIS), and Thermococcus celer RNA polymerase II subunit M ( Tc RPOM). The zinc‐ribbon structure of TFIIB, in conjunction with the biochemical analyses, suggests that residues on the β–sheet are involved in the interaction with RNA pol II/TFIIF, while the zinc‐binding site may increase the stability of the β–sheet.