Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR
Dynamic equilibrium on DNA defines transcriptional regulation of a multidrug binding transcriptional repressor, LmrR
复制标题
DNA 的动态平衡定义了多药结合转录抑制因子 LmrR 的转录调控
作者：
K. Takeuchi;Misaki Imai;I. Shimada
LmrR 是一种多药结合转录阻遏蛋白，可控制乳酸乳球菌中主要多药转运蛋白 LmrCD 的表达。混杂的复合连接使 LmrR 对 lmrCD 操纵子的亲和力降低数倍，以释放转录抑制；然而，亲和力的降低比典型转录抑制因子的亲和力降低要小几个数量级。在这里，我们发现 LmrR 的转录调控是通过体内操纵子结合状态和非特异性 DNA 吸附状态之间的平衡来实现的。在平衡状态下，lmrCD 操纵子的 LmrR 有效解离常数接近 LmrR 的内源浓度，这使得化合物连接时 LmrR 的占据量大幅减少。因此，LmrR代表了原核多药耐药系统转录调控的动态类型，其中化合物诱导的小亲和力降低通过非特异性DNA吸附与基因组DNA上的阻遏物的功能性重新定位相结合。
LmrR is a multidrug binding transcriptional repressor that controls the expression of a major multidrug transporter, LmrCD, in Lactococcus lactis. Promiscuous compound ligations reduce the affinity of LmrR for the lmrCD operator by several fold to release the transcriptional repression; however, the affinity reduction is orders of magnitude smaller than that of typical transcriptional repressors. Here, we found that the transcriptional regulation of LmrR is achieved through an equilibrium between the operator-bound and non-specific DNA-adsorption states in vivo. The effective dissociation constant of LmrR for the lmrCD operator under the equilibrium is close to the endogenous concentration of LmrR, which allows a substantial reduction of LmrR occupancy upon compound ligations. Therefore, LmrR represents a dynamic type of transcriptional regulation of prokaryotic multidrug resistance systems, where the small affinity reduction induced by compounds is coupled to the functional relocalization of the repressor on the genomic DNA via nonspecific DNA adsorption.
影响因子：
15.9
作者：
Ma, Dzwokai;Cook, David N.;Nikaido, Hiroshi
通讯作者：
Nikaido, Hiroshi