The involvement of transport proteins in transcriptional and metabolic regulation - PubMed (original) (raw)

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The involvement of transport proteins in transcriptional and metabolic regulation

Ake Västermark et al. Curr Opin Microbiol. 2014 Apr.

Abstract

Transport proteins have sometimes gained secondary regulatory functions that influence gene expression and metabolism. These functions allow communication with the external world via mechanistically distinctive signal transduction pathways. In this brief review we focus on three transport systems in Escherichia coli that control and coordinate carbon, exogenous hexose-phosphate and phosphorous metabolism. The transport proteins that play central roles in these processes are: first, the phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS), second, the glucose-6-phosphate receptor, UhpC, and third, the phosphate-specific transporter, PstSABC, respectively. While the PTS participates in multiple complex regulatory processes, three of which are discussed here, UhpC and the Pst transporters exemplify differing strategies.

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Figures

Fig. 1

Fig. 1. PTS-mediated catabolite repression and inducer exclusion

Principal signal transduction pathways for carbon regulation in E. coli. A sugar such as glucose (Glc) is transported into the cell cytoplasm and concomitantly phosphorylated by the PTS, resulting in dephosphorylation of IIAGlc. Non-phosphorylated IIAGlc inhibits non-PTS sugar catabolic enzymes and transporters causing inducer exclusion. Phosphorylated IIAGlc, on the other hand, promotes cAMP formation by binding to adenylate cyclase and allosterically activating it. cAMP-driven transcription results when cAMP binds to CRP, a transcriptional activator. The rate-limiting step in the PTS phosphoryl transfer chain appears to be Enzyme I-catalyzed phosphorylation of HPr. ⊥, inhibition; →, activation.

Fig. 2

Fig. 2. Regulation of glycogen breakdown by HPr of the PTS

HPr, the phosphate donor to PTS IIA proteins, becomes dephosphorylated when exogenous PTS sugars such as glucose are available. Dephospho-HPr then binds to glycogen phosphorylase, preventing glucose-1-phosphate release from glycogen. ⊥, inhibition.

Fig. 3

Fig. 3. Direct binding of a transcriptional repressor, Mlc, to the PTS Glucose Enzyme II

IIBCGlc in the unphosphorylated state (ie., when glucose is present) sequesters Mlc, preventing repression of pts genes. However, when glucose is absent, IIBCGlc is phosphorylated, causing release of Mlc so it represses expression of these genes. ⊥, repression.

Fig. 4

Fig. 4. The uptake hexose phosphate (UHP) transport system

The Uhp system consists of four proteins: UhpA, B, C, and T. UhpC and UhpT are homologous members of the major facilitator superfamily, serving the function of receptor/transporter and transporter, respectively. UhpB and A are the sensor kinase and response regulator of the regulatory two component system, serving to convey the signal of glucose-6-phosphate (G6P) availability to upregulate the expression of the uhpT gene. The 2 TMS membrane domain of the UhpB protein senses when the substrate, G6P, for which UhpC is highly specific, is bound to its external surface. Then with G6P bound to UhpC, and with UhpC in direct contact with UhpB, UhpB utilizes ATP to autophosphorylate its central domain. Once UhpB is phosphorylated, UhpB can donate its phosphoryl group to UhpA, which binds to multiple sites between -80 and -32 upstream of the start site of the uhpT gene, functioning as an enhancer in the promoter region. →, transcriptional activation.

Fig 5

Fig 5. The phosphate-specific transporter, PstSABC, a transporter functioning in signal transduction

The phosphate (pho) regulon uses PstS, a periplasmic inorganic phosphate (Pi) binding receptor that serves as a constituent of the ABC transport complex, PstSABC. It also serves as a sensor of external Pi concentration. PstS senses the phosphate concentration in the periplasmic space, transmits a signal via PstABC and PhoU to the sensor kinase, PhoR, independently of the transport activity of PstSABC, thereby influencing expression of pho regulon genes. Therefore, the transporter is a sensor that senses extracellular phosphate to control gene expression. ⊥, inhibition; →, activation.

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