The solution structure of the human ETS1-DNA complex reveals a novel mode of binding and true side chain intercalation

AbstractThe solution structure of a 24.4 kDa specific complex of the DNA-binding domain (DBD) of the human ETS1 (hETSi) oncoprotein with a 17-mer DNA has been solved by NMR. The interaction of the hETSi DBD with DNA reveals a surprising twist on the general features of helix-turn-helix (HTH)-DNA interactions. Major groove recognition involves the C-terminal two thirds of the HTH recognition helix, while minorgroove recognition occurs via true intercalation of the side chain of Trp-28, which extends from the minor to the major groove. This results in a sharp kink of ∼60° and a widening of the minor groove over one-half turn of the DNA. The orientation of the HTH element of the hETSi DBD with respect to the major groove is significantly rotated relative to other HTH proteins. These observations establish the ETS family of DNA-binding proteins as a distinct family of HTH proteins