Drastic Differences in Crh and HPr Synthesis Levels Reflect Their Different Impacts on Catabolite Repression in
            <i>Bacillus subtilis</i>

Görke, Boris; Fraysse, Laetitia; Galinier, Anne

doi:10.1128/jb.186.10.2992-2995.2004

Cited by 27 publications

(24 citation statements)

References 18 publications

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“…However, although our antiserum readily detected purified Crh protein, no signals were obtained in cell extracts (data not shown). This observation is in agreement with our previous data suggesting that Crh is present in the cell in much lower amounts than HPr (14). In conclusion, the cellular amounts of the global CCR regulators HPrK/P, CcpA, and HPr are not affected by the carbon source.…”

Section: Ccr Of ␤-Xylosidase Exerted By Different Carbon Sourcessupporting

confidence: 82%

Carbon Catabolite Repression in Bacillus subtilis : Quantitative Analysis of Repression Exerted by Different Carbon Sources

et al. 2008

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In many bacteria glucose is the preferred carbon source and represses the utilization of secondary substrates. In Bacillus subtilis, this carbon catabolite repression (CCR) is achieved by the global transcription regulator CcpA, whose activity is triggered by the availability of its phosphorylated cofactors, HPr(Ser46-P) and Crh(Ser46-P). Phosphorylation of these proteins is catalyzed by the metabolite-controlled kinase HPrK/P. Recent studies have focused on glucose as a repressing substrate. Here, we show that many carbohydrates cause CCR. The substrates form a hierarchy in their ability to exert repression via the CcpA-mediated CCR pathway. Of the two cofactors, HPr is sufficient for complete CCR. In contrast, Crh cannot substitute for HPr on substrates that cause a strong repression. Determination of the phosphorylation state of HPr in vivo revealed a correlation between the strength of repression and the degree of phosphorylation of HPr at Ser46. Sugars transported by the phosphotransferase system (PTS) cause the strongest repression. However, the phosphorylation state of HPr at its His15 residue and PTS transport activity have no impact on the global CCR mechanism, which is a major difference compared to the mechanism operative in Escherichia coli. Our data suggest that the hierarchy in CCR exerted by the different substrates is exclusively determined by the activity of HPrK/P.

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Section: Ccr Of ␤-Xylosidase Exerted By Different Carbon Sourcessupporting

confidence: 82%

Carbon Catabolite Repression in Bacillus subtilis : Quantitative Analysis of Repression Exerted by Different Carbon Sources

et al. 2008

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“…Whereas repression of citM by glucose is mediated via CcpA in complex with either P-Ser-HPr or P-Ser-Crh, repression by glutamate/succinate completely disappeared in a crh-disrupted strain (934). Interestingly, crh expression, which is much weaker than ptsH expression, is highest in cells grown on one of the two TCA cycle intermediates, citrate or succinate (286).…”

Section: Vol 70 2006 Phosphotransferase System-related Phosphorylatmentioning

confidence: 93%

How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria

Deutscher

Francke

Postma

2006

Microbiol Mol Biol Rev

1,188

769

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SUMMARY The phosphoenolpyruvate(PEP):carbohydrate phosphotransferase system (PTS) is found only in bacteria, where it catalyzes the transport and phosphorylation of numerous monosaccharides, disaccharides, amino sugars, polyols, and other sugar derivatives. To carry out its catalytic function in sugar transport and phosphorylation, the PTS uses PEP as an energy source and phosphoryl donor. The phosphoryl group of PEP is usually transferred via four distinct proteins (domains) to the transported sugar bound to the respective membrane component(s) (EIIC and EIID) of the PTS. The organization of the PTS as a four-step phosphoryl transfer system, in which all P derivatives exhibit similar energy (phosphorylation occurs at histidyl or cysteyl residues), is surprising, as a single protein (or domain) coupling energy transfer and sugar phosphorylation would be sufficient for PTS function. A possible explanation for the complexity of the PTS was provided by the discovery that the PTS also carries out numerous regulatory functions. Depending on their phosphorylation state, the four proteins (domains) forming the PTS phosphorylation cascade (EI, HPr, EIIA, and EIIB) can phosphorylate or interact with numerous non-PTS proteins and thereby regulate their activity. In addition, in certain bacteria, one of the PTS components (HPr) is phosphorylated by ATP at a seryl residue, which increases the complexity of PTS-mediated regulation. In this review, we try to summarize the known protein phosphorylation-related regulatory functions of the PTS. As we shall see, the PTS regulation network not only controls carbohydrate uptake and metabolism but also interferes with the utilization of nitrogen and phosphorus and the virulence of certain pathogens.

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“…Interestingly, Crh-Ser 46 -P can only partially substitute for HPr-Ser46-P in CCR, whereas HPr-Ser 46 -P can completely substitute for Crh-Ser 46 -P in this pathway (28,32). These findings appear to be explained by the finding that HPr is produced much more efficiently than Crh under strong conditions of CCR, resulting in up to 100-fold more HPr than Crh (33). Indeed, when bacteria utilize succinate or citrate as their major carbon source, the difference in HPr and Crh levels is only ϳ10-fold and under these conditions citM, a gene encoding the Mg 2ϩ -citrate transporter, is specifically repressed by Crh but not by HPr (33).…”

Section: Carbon Catabolite Repression/regulation (Ccr)mentioning

confidence: 79%

Phosphoprotein Crh-Ser46-P Displays Altered Binding to CcpA to Effect Carbon Catabolite Regulation

Schumacher

Seidel

Hillen

et al. 2006

Journal of Biological Chemistry

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In Gram-positive bacteria, the catabolite control protein A (CcpA) functions as the master transcriptional regulator of carbon catabolite repression/regulation (CCR). To effect CCR, CcpA binds a phosphoprotein, either HPr-Ser 46 -P or Crh-Ser 46 -P. Although Crh and histidine-containing protein (HPr) are structurally homologous, CcpA binds Crh-Ser 46 -P more weakly than HPr-Ser 46 -P. Moreover, Crh can form domain-swapped dimers, which have been hypothesized to be functionally relevant in CCR. To understand the molecular mechanism of Crh-Ser 46 -P regulation of CCR, we determined the structure of a CcpA-(Crh-Ser 46 -P)-DNA complex. The structure reveals that Crh-Ser 46 -P does not bind CcpA as a dimer but rather interacts with CcpA as a monomer in a manner similar to that of HPr-Ser 46 -P. The reduced affinity of Crh-Ser 46 -P for CcpA as compared with that of HPr-Ser 46 P is explained by weaker CrhSer 46 -P interactions in its contact region I to CcpA, which causes this region to shift away from CcpA. Nonetheless, the interface between CcpA and helix ␣2 of the second contact region (contact region II) of Crh-Ser 46 -P is maintained. This latter finding demonstrates that this contact region is necessary and sufficient to throw the allosteric switch to activate cre binding by CcpA. Carbon catabolite repression/regulation (CCR)2 is a global regulatory mechanism utilized by bacteria to select, out of a mixture of compounds, the carbon source providing the optimal growth advantage (1-3). CCR is mediated largely at the level of transcription. The master transcriptional regulator of CCR in bacilli and other Gram-positive bacteria with low GC content is the catabolite control protein A (CcpA) (4 -10). CcpA binds to catabolite responsive elements (cre) to mediate its effect (11,12). Approximately 10% of the Bacillus subtilis genome is under regulation by CcpA, underscoring its vital metabolic role (13).CcpA is a member of the LacI-GalR family of transcription regulators (14). LacI-GalR proteins contain a 60-residue N-terminal DNA binding domain that connects to a larger C-terminal domain. The C-terminal domain consists of N-and C-subdomains connected by a hinge region. (6, 24 -26). The recent structure of the CcpA-(HPr-Ser 46 -P)-cre revealed the mechanism by which HPr-Ser 46 -P functions as a corepressor for CcpA (27). Strikingly, this DNA binding activation mechanism is different from those of PurR and LacI in that CcpA utilizes a two-component phosphoprotein that is induced and stabilized by closure of its N-and C-subdomains. This mechanism involves both a rotation of CcpA subdomains as well as a relocation of the key residue Thr 61 , which is located at the interface of the DNAbinding and corepressor-binding domains. The repositioning of this residue leads to a juxtaposition of the DNA-binding domains to permit hinge helix formation in the presence of cognate DNA (15, 16).In addition to HPr, a structural and functional homologue, Crh (for catabolite repression HPr) has been identified, but only in bacilli (28). Crh...

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Drastic Differences in Crh and HPr Synthesis Levels Reflect Their Different Impacts on Catabolite Repression in Bacillus subtilis

Cited by 27 publications

References 18 publications

Carbon Catabolite Repression in Bacillus subtilis : Quantitative Analysis of Repression Exerted by Different Carbon Sources

Carbon Catabolite Repression in Bacillus subtilis : Quantitative Analysis of Repression Exerted by Different Carbon Sources

How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria

Phosphoprotein Crh-Ser46-P Displays Altered Binding to CcpA to Effect Carbon Catabolite Regulation

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