Schumacher M A, Choi K Y, Lu F, Zalkin H, Brennan R G
Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098, USA.
Cell. 1995 Oct 6;83(1):147-55. doi: 10.1016/0092-8674(95)90243-0.
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 A resolution. In the unliganded state, structural changes in the corepressor-binding pocket cause each subunit to rotate open by as much as 23 degrees, the consequences of which are the disengagement of the minor groove-binding hinge helices and repressor-DNA dissociation.
小分子效应物对同源DNA位点的结合可调节DNA结合蛋白的亲和力，这在原核生物和真核生物中都很常见。然而，从结构上看，效应物与一个结构域的结合如何影响远端结构域与DNA的结合，目前还知之甚少。在最初旨在深入了解乳糖阻遏物家族效应物调节DNA结合机制的研究中，我们确定了与共阻遏物和purF操纵基因结合的嘌呤阻遏物的晶体结构。为了进一步加深理解，我们以2.2埃的分辨率确定了嘌呤阻遏物无共阻遏物的共阻遏物结合结构域的结构。在未结合配体的状态下，共阻遏物结合口袋中的结构变化导致每个亚基最多旋转打开23度，其结果是小沟结合铰链螺旋脱离以及阻遏物与DNA解离。
