A folding transition and novel zinc finger accessory domain in the transcription factor ADR1

The region responsible for sequence-specific DNA binding by the transcripti on factor ADR1 contains two Cys(2)-His(2) zinc fingers and an additional N- terminal proximal accessory region (PAR), The N-terminal (non-finger) PAR i s unstructured in the absence of DNA and undergoes a folding transition on binding the DNA transcription target site, We have used a set of HN-HN NOEs derived from a perdeuterated protein-DNA complex to describe the fold of A DR1 bound to the UAS1 binding site. The PAR forms a compact domain consisti ng of three antiparallel strands that contact A-T base pairs in the major g roove, The three-strand domain is a novel fold among all known DNA-binding proteins. The PAR shares sequence homology with the N-terminal regions of o ther zinc finger proteins, suggesting that it represents a new DNA-binding module that extends the binding repertoire of zinc finger proteins.