MULTIPLE OLIGOMERIC STATES REGULATE THE DNA-BINDING OF HELIX-LOOP-HELIX PEPTIDES

To study the protein-protein interactions that allow Id, a negative re gulator of cell differentiation, to inhibit the DNA-binding activities of MyoD and E47, we have synthesized peptides corresponding to the he lix-loop-helix domains of MyoD, E47, and Id. We show that Id preferent ially inhibits the sequence-specific DNA-binding activity of MyoD, a m uscle-specific protein, as compared to E47, a more ubiquitous protein. The Id helix-loop-helix domain itself forms stable tetramers, and its inhibitory activity arises from the formation of a heterotetrameric s tructure with MyoD. The formation of this higher order complex provide s a general mechanism by which inhibitory proteins can generate suffic ient interaction free energy to overcome the large DNA-binding free en ergy of dimeric DNA-binding proteins.