THE SOLUTION STRUCTURE OF THE HUMAN ETS1-DNA COMPLEX REVEALS A NOVEL MODE OF BINDING AND TRUE SIDE-CHAIN INTERCALATION

The solution structure of a 24.4 kDa specific complex of the DNA-bindi ng domain (DBD) of the human ETS1 (hETS1) oncoprotein with a 17-mer DN A has been solved by NMR. The interaction of the hETS1 DBD with DNA re veals a surprising twist on the general features of helix-turn-helix ( HTH)-DNA interactions, Major groove recognition involves the C-termina l two thirds of the HTH recognition helix, while minor groove recognit ion occurs via true intercalation of the side chain of Trp-28, which e xtends from the minor to the major groove. This results in a sharp kin k of similar to 60 degrees and a widening of the minor groove over one -half turn of the DNA. The orientation of the HTH element of the hETS1 DBD with respect to the major groove is significantly rotated relativ e to other HTH proteins. These observations establish the ETS family o f DNA-binding proteins as a distinct family of HTH proteins.