Nègre D, Oudot C, Prost J F, Murakami K, Ishihama A, Cozzone A J, Cortay J C
Institut de Biologie et Chimie des Protéines, Centre National de la Recherche Scientifique, Lyon, France.
J Mol Biol. 1998 Feb 20;276(2):355-65. doi: 10.1006/jmbi.1997.1548.
The start site of transcription of the ppsA gene, whose expression is controlled by the regulatory protein FruR in Escherichia coli, was determined by primer extension of in vivo transcripts. The interactions of the ppsA promoter with either RNA polymerase or FruR factor were analysed by the base removal method. Our results indicate that: (i) the RNA polymerase binding site has a -10 extended module but lacks its -35 hexamer; (ii) FruR binds to a target DNA region centered around position -45.5 upstream of the ppsA gene. In addition, circular permutation analysis showed that, upon binding to its site, FruR induces a sharp bend of 120 degrees in the DNA helix, which suggests a crucial involvement of FruR-induced bending in ppsA promoter activation. Direct contacts between the upstream activating DNA and RNA polymerase were studied in an in vitro transcription assay by using reconstituted RNA polymerase mutants containing Ala substitutions in C-terminal domain of their alpha subunit. The alpha[L262A], alpha[R265A] and alpha[N268A] substitutions, which caused the most drastic reduction in the FruR-mediated activation of the ppsA promoter, had previously been shown to inhibit the upstream element-mediated activation at the rrnBP1 promoter.
在大肠杆菌中,ppsA基因的表达受调控蛋白FruR的控制,其转录起始位点通过体内转录本的引物延伸法确定。采用碱基去除法分析了ppsA启动子与RNA聚合酶或FruR因子的相互作用。我们的结果表明:(i)RNA聚合酶结合位点有一个-10延伸模块,但缺少-35六聚体;(ii)FruR结合到ppsA基因上游约-45.5位置周围的靶DNA区域。此外,环状置换分析表明,FruR与其位点结合后,会使DNA螺旋产生120度的急剧弯曲,这表明FruR诱导的弯曲在ppsA启动子激活中起关键作用。通过使用在其α亚基C末端结构域含有丙氨酸替代的重组RNA聚合酶突变体,在体外转录试验中研究了上游激活DNA与RNA聚合酶之间的直接接触。α[L262A]、α[R265A]和α[N268A]替代导致ppsA启动子的FruR介导的激活最显著降低,此前已证明这些替代会抑制rrnBP1启动子的上游元件介导的激活。