The modulation of the affinity of DNA-binding proteins by small molecule effectors for cognate DNA sites is common to both prokaryotes and eukaryotes. However, the mechanisms by which effector binding to one domain affects DNA binding by a distal domain are poorly understood structurally. In initial studies to provide insight into the mechanism of effector-modulated DNA binding of the lactose repressor family, we determined the crystal structure of the purine repressor bound to a corepressor and purF operator. To extend our understanding, we have determined the structure of the corepressor-free corepressor-binding domain of the purine repressor at 2.2 Å resolution. In the unliganded state, structural changes in the corepressorbinding pocket cause each subunit to rotate open by as much as 23°, the consequences of which are the disengagement of the minor groove-binding hinge helices and repressor-DNA dissociation.
Bibliographical noteFunding Information:
Correspondence should be addressed to R. G. B. The coordinates are in the process of being deposited in the Brookhaven Protein Data Bank but are available from R. G. B. at email@example.com. R. G. B. was supported by March of Dimes grant 847 and by Public Health Service grant GM-49244. M. A. S. was supported by a National Defense Science and Engineering Graduate Fellowship in Biosciences. H. 2. was supported by Public Health Service grant GM-24658.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)