The Bacterial Phosphoenolpyruvate:Carbohydrate Phosphotransferase System: Regulation by Protein Phosphorylation and Phosphorylation-Dependent Protein-Protein Interactions

Abstract

SUMMARY The bacterial phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS) carries out both catalytic and regulatory functions. It catalyzes the transport and phosphorylation of a variety of sugars and sugar derivatives but also carries out numerous regulatory functions related to carbon, nitrogen, and phosphate metabolism, to chemotaxis, to potassium transport, and to the virulence of certain pathogens. For these different regulatory processes, the signal is provided by the phosphorylation state of the PTS components, which varies according to the availability of PTS substrates and the metabolic state of the cell. PEP acts as phosphoryl donor for enzyme I (EI), which, together with HPr and one of several EIIA and EIIB pairs, forms a phosphorylation cascade which allows phosphorylation of the cognate carbohydrate bound to the membrane-spanning EIIC. HPr of firmicutes and numerous proteobacteria is also phosphorylated in an ATP-dependent reaction catalyzed by the bifunctional HPr kinase/phosphorylase. PTS-mediated regulatory mechanisms are based either on direct phosphorylation of the target protein or on phosphorylation-dependent interactions. For regulation by PTS-mediated phosphorylation, the target proteins either acquired a PTS domain by fusing it to their N or C termini or integrated a specific, conserved PTS regulation domain (PRD) or, alternatively, developed their own specific sites for PTS-mediated phosphorylation. Protein-protein interactions can occur with either phosphorylated or unphosphorylated PTS components and can either stimulate or inhibit the function of the target proteins. This large variety of signal transduction mechanisms allows the PTS to regulate numerous proteins and to form a vast regulatory network responding to the phosphorylation state of various PTS components.

Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli

“…10). In addition, the phosphorylation state of the PTS protein EIIA Glc serves as the key sensory mechanism for cAMP synthesis and catabolite repression control and for the turnover pathway of CsrB/C sRNAs (43,44,48). Our present data establish direct and apparently indirect connections between these two important global regulatory systems.…”

“…Under conditions of carbon limitation, the PTS proteins, including the glucose-specific protein EIIA Glc , are predominantly phosphorylated. In this form, P-EIIA Glc binds to adenylate cyclase and activates cAMP synthesis (48). Transport and phosphorylation of glucose or other PTS sugars leads to dephosphorylation of EIIA Glc and loss of its ability to activate cAMP synthesis.…”

Genomic insights into the uncultivated marine Zetaproteobacteria at Loihi Seamount

“…These genes were found across all OTUs with the exception of OTU 4 and include the mannose/fructose-specific component IIA and the Ntr-type mannitol/fructose-specific component IIA genes. As the phosphotransferase system genes may have a complex functional role in the cell (Deutscher et al, 2014), the specific role of these genes in the Zetaproteobacteria remains uncertain. Seven SAGs from three OTUs (1, 4 and 10) have endoglucanases, b-glucosidases, xylanases, and chitin deacetylases, suggesting that there is a genetic potential for degradation and utilization of complex carbohydrates.…”

Transcription of malP is subject to phosphotransferase system-dependent regulation in Corynebacterium glutamicum

“…Therefore, PTSs often possess, in addition to their catalytic function as importers of sugars and/or sugar derivatives, tasks within the control of diverse cellular functions, e.g. carbon metabolism, nitrogen metabolism, chemotaxis, biofilm formation and/or virulence (Deutscher et al, 2014;Gabor et al, 2011). To adjust metabolism to nutrient availability, expression of enzymes for transport and catabolism of less favourable substrates is often prevented in the presence of the preferred carbon source.…”

“…Inducer exclusion, the major CCR mechanism in E. coli and Salmonella enterica serovar Typhimurium, inhibits the utilization of, for example, lactose, glycerol and maltose in the presence of the PTS substrate glucose and requires EIIA Glc (enzyme IIA of the glucose PTS) as the central player (Deutscher et al, 2014;Görke & Stülke, 2008;Inada et al, 1996). EIIA Glc becomes dephosphorylated during the transport of readily metabolizable substrate glucose (Hogema et al, 1998).…”