Rampersaud A, Norioka S, Inouye M
Department of Biochemistry, Robert Wood Johnson Medical School, Rutgers, University of Medicine and Dentistry of New Jersey, Piscataway 08854.
J Biol Chem. 1989 Nov 5;264(31):18693-700.
In Escherichia coli the expression of the outer membrane porin gene ompF requires the transcriptional activator protein OmpR. Previous DNase I footprinting experiments with purified OmpR localized the OmpR binding site from positions -105 to -60 (relative to the transcriptional start site) in the ompF promoter, and three tandem 10-base pair sequences elements (Fa, Fb, and Fc) within this region were proposed to be important for OmpR recognition. In order to elucidate the roles of the F boxes for transcriptional activation of ompF, various F box deletions and point mutations were constructed and analyzed for their effects on ompF-lacZ expression and OmpR binding. Removal of 102 nucleotides, which included a portion of the OmpR binding region (the Fa box), evidenced the largest decrease in transcriptional activation and significantly reduced OmpR binding. Additional deletion of four more base pairs in this target site (representing half of the Fb box) further reduced ompF expression. OmpR interactions with DNA sequences representing the OmpR binding region were analyzed by DNA mobility shift experiments. A 43-base pair ompF oligonucleotide containing the Fa, Fb, and Fc regions was sufficient for OmpR-dependent DNA binding using either purified OmpR or cell supernatants. The central C residue in each F box was changed to a T and unique patterns of protein-DNA complexes were observed that were different from that of the wild type binding site. The most dramatic effect on OmpR binding was observed when the C to T transversion occurred in the Fb box, and this mutation also reduced the level of ompF-lacZ expression. Our results indicate that the F boxes play important roles in the activation of ompF expression, and we suggest that OmpR may interact cooperatively with these boxes.
在大肠杆菌中,外膜孔蛋白基因ompF的表达需要转录激活蛋白OmpR。先前使用纯化的OmpR进行的DNA酶I足迹实验将OmpR结合位点定位在ompF启动子中相对于转录起始位点的-105至-60位,并且该区域内的三个串联10碱基对序列元件(Fa、Fb和Fc)被认为对OmpR识别很重要。为了阐明F框对ompF转录激活的作用,构建了各种F框缺失和点突变,并分析了它们对ompF-lacZ表达和OmpR结合的影响。去除102个核苷酸,其中包括一部分OmpR结合区域(Fa框),证明转录激活下降幅度最大,并且显著降低了OmpR结合。在该靶位点再额外缺失四个碱基对(代表Fb框的一半)进一步降低了ompF表达。通过DNA迁移率变动实验分析了OmpR与代表OmpR结合区域的DNA序列的相互作用。使用纯化的OmpR或细胞上清液,包含Fa、Fb和Fc区域的43碱基对ompF寡核苷酸足以实现OmpR依赖的DNA结合。每个F框中的中心C残基被替换为T,观察到与野生型结合位点不同的独特蛋白质-DNA复合物模式。当Fb框中发生C到T的颠换时,观察到对OmpR结合的最显著影响,并且该突变也降低了ompF-lacZ表达水平。我们的结果表明,F框在ompF表达的激活中起重要作用,并且我们认为OmpR可能与这些框协同相互作用。