Group Translocation – PEP:PTS

Abstract

The phosphoenolpyruvate:carbohydrate phospho‐transferase system (PEP:PTS) is a prokaryotic enzyme/transport system that phosphorylates its extracellular carbohydrate substrates during transport, leading to intracellular accumulation of the sugar phosphate esters. Several phosphoryl transfer proteins play essential roles in sugar uptake, and they comprise a phosphoryl transfer chain using PEP as the phosphoryl donor, and the incoming sugar as the ultimate phosphoryl acceptor. This phosphoryl transfer chain is: PEP→EI→HPr→IIA→IIB+ IIC→sugar, where E=Enzyme and HPr=a small heat stable, histidine‐containing protein, and only the IIC constituent, the transport protein, is not phosphorylated. In mixtures of carbon sources, preferential growth on PTS substrates often occurs, as the phosphorylation state of PTS proteins coordinates the activities and synthesis of enzymes that initiate sugar metabolism. The mechanisms of regulation are different in representative Gram‐negative and Gram‐positive bacteria, but in both cases the PTS plays a central role. The PTS in Escherichia coli accomplishes this goal by regulating both cyclic adenosine monophosphate (AMP) synthesis and the uptake of sugar inducers of enzyme synthesis. It also plays a role in the coordination of nitrogen metabolism with carbon metabolism. In many bacteria, the PTS serves as a chemosensory system, directing movement of bacteria up concentration gradients of PTS sugars. In a few bacteria, the PTS functions in regulation but not in sugar uptake. Although this enzyme system has not been found in eukaryotes, it has been identified in archaea. The PTS is thus a multifunctional enzyme/transport/sensor/regulatory system that coordinates many activities in prokaryotic cells.

Key Concepts:

  • Biological membranes provide the fundamental barrier that separates the inside of a cell (the cytoplasm) from the extracellular space.

  • Embedded in these structures are proteins, many of which transport substances across the membrane.

  • The phosphotransferase system (PTS) serves as a complex transport system.

  • It consists of energy‐coupling enzymes (Enzymes I, HPr, IIA and IIB) as well as the PTS permeases (Enzymes IIC or IICs).

  • The IIC components couple phosphoryl transfer from IIB∼P to sugar substrate phosphorylation.

  • The process of coupled sugar uptake with sugar phosphorylation, involving substrate modification, is called ‘group translocation’.

  • The PTS serves as a chemoreception system, directing the activity of the bacterial flagellum so that bacteria swim up concentration gradients of nutrient sugars.

  • The PTS is a complex multifaceted system, regulating the activities of many non‐PTS enzymes and transporters, thereby creating a hierarchical system of carbon sources.

  • PTS protein domains are incorporated into many transcription factors, enzymes and transporters, allowing it to regulate these determinants of prokaryotic cell physiology and pathology.

  • A comprehensive understanding of prokaryotic cell biology requires a detailed understanding of the PTS.

Keywords: carbohydrate transport; catabolite repression; crr; diauxie; metabolic regulation; protein phosphorylation; PTS; evolution

Figure 1.

The phosphotransferase system (PTS). The general PTS proteins are Enzyme I (EI) and HPr. Only three of many carbohydrate‐specific EII complexes are shown: IICBAMtl is specific for mannitol; IICBGlc/IIAGlc for glucose; IIABMan/IICMan/IIDMan for mannose and other hexoses. The phosphorylated forms of EI and HPr are indicated, respectively, as P∼EI and P∼HPr. The phosphorylated forms of the IIA and IIB domains are also shown. PEP, phosphoenolpyruvate.

Figure 2.

Schematic depiction of the protein constituents of a typical PTS permease. A PTS permease is a sugar transporting Enzyme II complex of the bacterial PEP‐dependent phosphotransferase system. The sugar substrate (S) is transported from the extracellular medium through the membrane in a pathway determined by the integral membrane permease‐like Enzyme IIC (C) constituent, usually a homodimer in the membrane as shown. The sequentially acting energy‐coupling proteins transfer a phosphoryl group from the initial phosphoryl donor, phosphoenolpyruvate (PEP), to the ultimate phosphoryl acceptor, sugar, yielding a sugar‐phosphate (S‐P). These enzymes are: Enzyme I (I), HPr (H), Enzyme IIA (A) and Enzyme IIB (B). I is the first general energy‐coupling protein; H is the second general energy‐coupling protein; A is the indirect family‐specific phosphoryl donor; B is the direct permease‐specific phosphoryl donor; and C is the permease/receptor that energises transport of the sugar substrate. A given bacterial cell may possess multiple PTS Enzyme II complexes, each specific for a different set of sugars. Some bacteria also possess multiple sets of PTS energy‐coupling proteins (Enzymes I, HPr, IIA and IIB) that may play regulatory roles independently of sugar transport. Reproduced with permission from Saier et al., . © The Biochemical Society.

Figure 3.

Proposed pathway for the evolution of the currently recognised families that comprise the Glc‐Fru‐Lac (GFL) superfamily of the PTS. A primordial Fructose (Fru) Enzyme II permease complex is postulated. Reproduced with permission from Saier et al., . © The Biochemical Society.

Figure 4.

The glycolytic cycle as it occurs in bacteria such as E. coli. The cycle is drawn using the standard abbreviations of the glycolytic intermediates. The enzymes catalysing the different reactions shown in the figure are: (1) the PEP–glucose phosphotransferase system (PTS); (2) phosphoglucoisomerase (PGI); (3) phosphofructokinase (PFK); (4) aldolase; (5) triose phosphate isomerase (TPI); (6) glyceraldehyde‐3‐P dehydrogenase (G3PDH); (7) phosphoglycerate kinase (PGK); (8) phosphoglycerate mutase (PGM); (9) enolase; (10) pyruvate kinase (PK); and (11) PEP carboxylase. Reactions 1–9 comprise the glycolytic cycle. Double‐headed arrows indicate reversible reactions whereas single‐headed arrows indicate essentially irreversible reactions. Reaction 7 has a large negative ΔG′0 and is therefore indicated as being irreversible. However, this reaction can be considered to be reversible by virtue of the endergonic nature of the reactions preceding and following step 7.

Figure 5.

Regulation by the phosphotransferase system (PTS) in enteric bacteria. IIAGlc and P∼IIAGlc represent the dephosphorylated and phosphorylated forms of IIAGlc. P∼IIAGlc activates (+) adenylate cyclase, whereas IIAGlc inhibits (−) non‐PTS class I substrate transporters, denoted by S1 and S2. Other symbols as in Figure .

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Saier, Milton H, and Shlykov, Maksim A(Jan 2012) Group Translocation – PEP:PTS. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001423.pub2]