title: Interplay between CRP-cAMP and PII-Ntr systems forms novel regulatory network between carbon metabolism and nitrogen assimilation in Escherichia coli.
abstract: In Escherichia coli, utilization of carbon sources is regulated by the phosphoenolpyruvate-dependent phosphotransferase system (PTS), which modulates the intracellular levels of cAMP. The cAMP receptor protein (CRP) controls the transcription of many catabolic genes. The availability of nitrogen is sensed by the PII protein at the level of intracellular glutamine. Glutamine is transported mainly by GlnHPQ, and synthesized by glutamine synthetase (GS) encoded by glnA. Previous studies suggest that CRP affects nitrogen assimilation. Here we showed that at least two mechanisms are involved. First, CRP activates glnHp1 via synergistic binding with sigma 70 RNA polymerase (Esigma(70)) and represses glnHp2. As a consequence, in the presence of glutamine, the overall enhancement of glnHPQ expression alters GlnB signalling and de-activates glnAp2. Second, in vitro studies show that CRP can be recruited by sigma 54 holoenzyme (Esigma(54)) to a site centred at -51.5 upstream of glnAp2. CRP-induced DNA-bending prevents the nitrogen regulation protein C (NtrC) activator from approaching the activator-accessible face of the promoter-bound Esigma(54) closed complex, and inhibits glnAp2. Therefore, as the major transcriptional effector of the 'glucose effect', CRP affects both the signal transduction pathway and the overall geometry of the transcriptional machinery of components of the nitrogen regulon.
authors.affiliation: National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing 100871, PR China.
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Mao
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Huo
authors.forename: Martin
authors.initials: M
authors.lastname: Buck
authors.forename: Annie
authors.initials: A
authors.lastname: Kolb
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Wang
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D002244:Carbon / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D005974:Glutamate-Ammonia Ligase / Q000235:genetics; D005973:Glutamine / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism*; D009876:Operon; D051922:PII Nitrogen Regulatory Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012808:Sigma Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D026923:Amino Acid Transport Systems, Basic; D002373:Cyclic AMP Receptor Protein; D029968:Escherichia coli Proteins; D051922:PII Nitrogen Regulatory Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C481662:crp protein, E coli; D005973:Glutamine; D002244:Carbon; D000242:Cyclic AMP; C081775:RNA polymerase sigma 70; D012321:DNA-Directed RNA Polymerases; D005974:Glutamate-Ammonia Ligase; D009584:Nitrogen