Transcriptional Activity of the TFIIA Four-helix Bundle in Vivo

TFIIA contributes to transcription initiation by stabilizing the TBP-TATA interaction and by mediating the response to transcriptional activators and inhibitors. TFIIA contains a six-stranded beta-sheet domain and a four-helix bundle. The beta-domain makes functional contacts with DNA and TBP. The role of the four-helix bundle was investigated using a structure-based model of this domain (called 4HB). 4HB adopts a highly stable, helical fold, consistent with its structure in the context of TFIIA. Like TBP and other intact transcription factors, 4HB is able to activate transcription in vivo when artificially recruited to a promoter via a heterologous DNA-binding domain. Thus, in addition to making important contacts with TBP and DNA via the beta-domain, TFIIA makes other specific, functional contacts with the transcriptional machinery via the four-helix bundle. Proteins 2001;43:227-232.