MODULATION OF TRANSCRIPTION FACTOR ETS-1 DNA-BINDING - DNA-INDUCED UNFOLDING OF AN ALPHA-HELIX

Conformational changes, including local protein folding, play importan t roles in protein-DNA interactions. Here, studies of the transcriptio n factor Ets-1 provided evidence that local protein unfolding also can accompany DNA binding. Circular dichroism and partial proteolysis sho wed that the secondary structure of the Ets-1 DNA-binding domain is un changed in the presence of DNA. In contrast, DNA allosterically induce d the unfolding of an cr helix that lies within a flanking region invo lved in the negative regulation of DNA binding. These findings suggest a structural basis for the intramolecular inhibition of DNA binding a nd a mechanism for the cooperative partnerships that are common featur es of many eukaryotic transcription factors.