CRYSTAL-STRUCTURE OF TRANSCRIPTION FACTOR E47 - E-BOX RECOGNITION BY A BASIC REGION HELIX-LOOP-HELIX DIMER

A large group of transcription factors regulating cell growth and diff erentiation share a dimeric alpha-helical DNA-binding domain termed th e basic region helix-loop-helix (bHLH). bHLH proteins associate as hom odimers and heterodimers having distinctive DNA-binding activities and transcriptional activities that are central to the regulated differen tiation of a number of tissues. Some of the bHLH residues specifying t hese activities have been identified, but a full understanding of thei r function has awaited further structural information. We report here the crystal structure of the transcription factor E47 bHLH domain boun d to DNA. The bHLH of E47 is a parallel, four-helix bundle with struct ural features that distinguish it from the bHLH-zipper protein Max. Th e E47 dimer makes nonequivalent contacts to each half of the -CACCTG-b inding site. Sequence discrimination at the center of the E box may re sult from interaction with both the DNA bases and the phosphodiester b ackbone.