MECHANISM OF COREPRESSOR-MEDIATED SPECIFIC DNA-BINDING BY THE PURINE REPRESSOR

The modulation of the affinity of DNA-binding proteins by small molecu le effecters for cognate DNA sites is common to both prokaryotes and e ukaryotes. However, the mechanisms by which effector binding to one do main affects DNA binding by a distal domain are poorly understood stru cturally. In initial studies to provide insight into the mechanism of effector-modulated DNA binding of the lactose repressor family, we det ermined the crystal structure of the purine repressor bound to a corep ressor and purF operator. To extend our understanding, we have determi ned the structure of the corepressor-free corepressor-binding domain o f the purine repressor at 2.2 Angstrom resolution. In the unliganded s tate, structural changes in the corepressor-binding pocket cause each subunit to rotate open by as much as 23 degrees, the consequences of w hich are the disengagement of the minor groove-binding hinge helices a nd repressor-DNA dissociation.