A NEW PATTERN FOR HELIX-TURN-HELIX RECOGNITION REVEALED BY THE PU.1 ETS-DOMAIN-DNA COMPLEX

THE Ets family of transcription factors, of which there are now about 35 members(1,2), regulate gene expression during growth and developmen t. They share a conserved domain of around 85 amino acids(3) which bin ds as a monomer to the DNA sequence 5'-C/ AGGAA/T-3'. We have determin ed the crystal structure of an ETS domain complexed with DNA, at 2.3-A ngstrom resolution. The domain is similar to alpha + beta (winged) 'he lix-turn-helix' proteins and interacts with a ten-base-pair region of duplex DNA which takes up a uniform curve of 8 degrees. The domain con tacts the DNA by a novel loop-helix-loop architecture, Four of the ami no acids that directly interact with the DNA are highly conserved: two arginines from the recognition helix lying in the major groove, one l ysine from the 'wing' that binds upstream of the core GGAA sequence, a nd another lysine, from the 'turn' of the 'helix-turn-helix' motif, wh ich binds downstream and on the opposite strand.