-
Biochimica Et Biophysica Acta Mar 2011The twin-arginine translocation (Tat) system operates in plant thylakoid membranes and the plasma membranes of most free-living bacteria. In bacteria, it is responsible... (Review)
Review
The twin-arginine translocation (Tat) system operates in plant thylakoid membranes and the plasma membranes of most free-living bacteria. In bacteria, it is responsible for the export of a number of proteins to the periplasm, outer membrane or growth medium, selecting substrates by virtue of cleavable N-terminal signal peptides that contain a key twin-arginine motif together with other determinants. Its most notable attribute is its ability to transport large folded proteins (even oligomeric proteins) across the tightly sealed plasma membrane. In Gram-negative bacteria, TatABC subunits appear to carry out all of the essential translocation functions in the form of two distinct complexes at steady state: a TatABC substrate-binding complex and separate TatA complex. Several studies favour a model in which these complexes transiently coalesce to generate the full translocase. Most Gram-positive organisms possess an even simpler "minimalist" Tat system which lacks a TatB component and contains, instead, a bifunctional TatA component. These Tat systems may involve the operation of a TatAC complex together with a separate TatA complex, although a radically different model for TatAC-type systems has also been proposed. While bacterial Tat systems appear to require the presence of only a few proteins for the actual translocation event, there is increasing evidence for the operation of ancillary components that carry out sophisticated "proofreading" activities. These activities ensure that redox proteins are only exported after full assembly of the cofactor, thereby avoiding the futile export of apo-forms. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes.
Topics: Amino Acid Sequence; Arginine; Biological Transport; Escherichia coli; Escherichia coli Proteins; Membrane Transport Proteins; Molecular Sequence Data; Protein Sorting Signals; Protein Transport; Sequence Homology, Amino Acid
PubMed: 21126506
DOI: 10.1016/j.bbamem.2010.11.023 -
Drug Metabolism and Pharmacokinetics 2008We have recently identified a Na+/Cl--coupled transport system in mammalian cells for endogenous and synthetic opioid peptides. This transport system does not transport...
We have recently identified a Na+/Cl--coupled transport system in mammalian cells for endogenous and synthetic opioid peptides. This transport system does not transport dipeptides/tripeptides, but is stimulated by these small peptides. Here we investigated the influence of L-kyotorphin (L-Tyr-L-Arg), an endogenous dipeptide with opioid activity, on this transport system. The activity of the transport system, measured in SK-N-SH cells (a human neuronal cell line) with deltorphin II as a model substrate, was stimulated approximately 2.5-fold by L-kyotorphin, with half-maximal stimulation occurring at approximately 100 microM. The stimulation was associated primarily with an increase in the affinity for deltorphin II. The stimulation caused by L-kyotorphin was stereospecific; L-Tyr-D-Arg (D-kyotorphin) had minimal effect. The influence of L-kyotorphin was observed also in a different cell line which expressed the opioid peptide transport system. While L-kyotorphin is a stimulator of opioid peptide transport, it is a transportable substrate for the H+-coupled peptide transporter PEPT2, which is expressed widely in the brain. Since the activity of the opioid peptide transport system is modulated by extracellular L-kyotorphin and since PEPT2 is an important determinant of extracellular L-kyotorphin in the brain, the expression/activity of PEPT2 may be a critical factor in the modulation of opioidergic neurotransmission in vivo.
Topics: Animals; Biological Transport; Cell Line; Chlorides; Dose-Response Relationship, Drug; Endorphins; Humans; Oligopeptides; Opioid Peptides; Sodium; Stereoisomerism; Symporters; Xenopus laevis
PubMed: 18762712
DOI: 10.2133/dmpk.23.254 -
Planta Mar 2022A critical investigation into arsenic uptake and transportation, its phytotoxic effects, and defense strategies including complex signaling cascades and regulatory... (Review)
Review
A critical investigation into arsenic uptake and transportation, its phytotoxic effects, and defense strategies including complex signaling cascades and regulatory networks in plants. The metalloid arsenic (As) is a leading pollutant of soil and water. It easily finds its way into the food chain through plants, more precisely crops, a common diet source for humans resulting in serious health risks. Prolonged As exposure causes detrimental effects in plants and is diaphanously observed through numerous physiological, biochemical, and molecular attributes. Different inorganic and organic As species enter into the plant system via a variety of transporters e.g., phosphate transporters, aquaporins, etc. Therefore, plants tend to accumulate elevated levels of As which leads to severe phytotoxic damages including anomalies in biomolecules like protein, lipid, and DNA. To combat this, plants employ quite a few mitigation strategies such as efficient As efflux from the cell, iron plaque formation, regulation of As transporters, and intracellular chelation with an array of thiol-rich molecules such as phytochelatin, glutathione, and metallothionein followed by vacuolar compartmentalization of As through various vacuolar transporters. Moreover, the antioxidant machinery is also implicated to nullify the perilous outcomes of the metalloid. The stress ascribed by the metalloid also marks the commencement of multiple signaling cascades. This whole complicated system is indeed controlled by several transcription factors and microRNAs. This review aims to understand, in general, the plant-soil-arsenic interaction, effects of As in plants, As uptake mechanisms and its dynamics, and multifarious As detoxification mechanisms in plants. A major portion of this article is also devoted to understanding and deciphering the nexus between As stress-responsive mechanisms and its underlying complex interconnected regulatory networks.
Topics: Arsenic; Biological Transport; Crops, Agricultural; Membrane Transport Proteins; Phytochelatins
PubMed: 35303194
DOI: 10.1007/s00425-022-03869-4 -
Journal of Bacteriology Apr 2018Pyruvate is an important intermediate of central carbon metabolism and connects a variety of metabolic pathways in Although the intracellular pyruvate concentration is...
Pyruvate is an important intermediate of central carbon metabolism and connects a variety of metabolic pathways in Although the intracellular pyruvate concentration is dynamically altered and tightly balanced during cell growth, the pyruvate transport system remains unclear. Here, we identified a pyruvate transporter in using high-throughput transposon sequencing. The transposon mutant library (a total of 5 × 10 mutants) was serially grown with a toxic pyruvate analog (3-fluoropyruvate [3FP]) to enrich for transposon mutants lacking pyruvate transport function. A total of 52 candidates were selected on the basis of a stringent enrichment level of transposon insertion frequency in response to 3FP treatment. Subsequently, their pyruvate transporter function was examined by conventional functional assays, such as those measuring growth inhibition by the toxic pyruvate analog and pyruvate uptake activity. The pyruvate transporter system comprises CstA and YbdD, which are known as a peptide transporter and a conserved protein, respectively, whose functions are associated with carbon starvation conditions. In addition to the presence of more than one endogenous pyruvate importer, it has been suggested that the genome encodes constitutive and inducible pyruvate transporters. Our results demonstrated that CstA and YbdD comprise the constitutive pyruvate transporter system in , which is consistent with the tentative genomic locus previously suggested and the functional relationship with the extracellular pyruvate sensing system. The identification of this pyruvate transporter system provides valuable genetic information for understanding the complex process of pyruvate metabolism in Pyruvate is an important metabolite as a central node in bacterial metabolism, and its intracellular levels are tightly regulated to maintain its functional roles in highly interconnected metabolic pathways. However, an understanding of the mechanism of how bacterial cells excrete and transport pyruvate remains elusive. Using high-throughput transposon sequencing followed by pyruvate uptake activity testing of the selected candidate genes, we found that a pyruvate transporter system comprising CstA and YbdD, currently annotated as a peptide transporter and a conserved protein, respectively, constitutively transports pyruvate. The identification of the physiological role of the pyruvate transporter system provides valuable genetic information for understanding the complex pyruvate metabolism in .
Topics: Biological Transport; DNA Transposable Elements; Escherichia coli; Escherichia coli Proteins; Gene Expression Regulation, Bacterial; Genes, Bacterial; High-Throughput Nucleotide Sequencing; Membrane Transport Proteins; Monocarboxylic Acid Transporters; Pyruvic Acid; Trans-Activators
PubMed: 29358499
DOI: 10.1128/JB.00771-17 -
Current Opinion in Nephrology and... Mar 2011This review aims to describe the recent findings concerning novel Mg transporters as putative interesting players in renal transepithelial Mg transport. (Review)
Review
PURPOSE OF REVIEW
This review aims to describe the recent findings concerning novel Mg transporters as putative interesting players in renal transepithelial Mg transport.
RECENT FINDINGS
So far, the best characterized Mg transport proteins are found in prokaryotes and yeast cells. In recent years, phylogenetic analysis and differential gene expression studies have led to the identification of numerous genes associated with Mg transport in eukaryotes. In addition to the well known transient receptor potential channel melastatin (TRPM), members 6 and 7, and the mitochondrial transporter Mrs2, additional Mg-transporting protein families can be acknowledged including the magnesium (Mag) transporters, the solute carrier (SLC) family 41 members, ancient conserved domain proteins (ACDP), nonimprinted in Prader-Willi/Angelman syndrome (NIPA) proteins, membrane Mg transporters (MMgT) and huntingtin-interacting protein 14 (HIP14).
SUMMARY
The identification of several mammalian proteins involved in Mg transport highlights the physiological importance of this cation and its tight regulation in numerous tissues. Further investigation of these transporters might represent a key tool to complement our current knowledge about renal Mg handling.
Topics: Acyltransferases; Adaptor Proteins, Signal Transducing; Animals; Biological Transport; Cation Transport Proteins; Homeostasis; Humans; Kidney; Magnesium; Nerve Tissue Proteins; TRPM Cation Channels
PubMed: 21191290
DOI: 10.1097/MNH.0b013e3283435ee4 -
Proceedings of the National Academy of... Jun 2001
Topics: Adenosine Triphosphatases; Animals; Biological Transport; Carrier Proteins; Cation Transport Proteins; Copper; Copper Transport Proteins; Copper Transporter 1; Copper-Transporting ATPases; Humans; Iron; Membrane Proteins; Metallochaperones; Mice; Molecular Chaperones; Neuropeptides; Recombinant Fusion Proteins; X Chromosome
PubMed: 11390990
DOI: 10.1073/pnas.131192498 -
Molecular Microbiology May 2020The twin-arginine protein transport (Tat pathway) is found in prokaryotes and plant organelles and transports folded proteins across membranes. Targeting of substrates... (Review)
Review
The twin-arginine protein transport (Tat pathway) is found in prokaryotes and plant organelles and transports folded proteins across membranes. Targeting of substrates to the Tat system is mediated by the presence of an N-terminal signal sequence containing a highly conserved twin-arginine motif. The Tat machinery comprises membrane proteins from the TatA and TatC families. Assembly of the Tat translocon is dynamic and is triggered by the interaction of a Tat substrate with the Tat receptor complex. This review will summarise recent advances in our understanding of Tat transport, focusing in particular on the roles played by Tat signal peptides in protein targeting and translocation.
Topics: Amino Acid Motifs; Bacterial Proteins; Cell Membrane; Escherichia coli Proteins; Membrane Transport Proteins; Protein Binding; Protein Conformation; Protein Sorting Signals; Protein Transport; Twin-Arginine-Translocation System
PubMed: 31971282
DOI: 10.1111/mmi.14461 -
European Journal of Immunology Aug 1996The heterodimeric transporter associated with antigen processing (TAP1/TAP2) translocates peptides from the cytosol into the endoplasmic reticulum where loading of major...
The heterodimeric transporter associated with antigen processing (TAP1/TAP2) translocates peptides from the cytosol into the endoplasmic reticulum where loading of major histocompatibility complex class I molecules takes place. TAP transporters from different species are known to exhibit distinct transport specificities with regard to the C-terminal amino acid (aa) of peptides. Thus, human TAP (hTAP), and rat TAP (rTAP) containing the rTAP2a allele are rather promiscuous, whereas mouse TAP (mTAP), and rTAP containing the rTAP2a allele are restrictive and select against peptides with C-terminal small polar/hydrophobic or positively charged aa. The structural basis for this selectivity is not clear. To assess the relative contribution of the TAP1 and TAP2 subunits to transport specificity, we have constructed and analyzed interspecies TAP hybrids and point mutants of hTAP2 expressed in Sf9 insect cells and in TAP-deficient T2 cells. Transport assays with 20 C-terminal variants of the peptide RYWANATRSX showed that: first, transport specificity with regard to C-terminal aa is mainly influenced by TAP2, but TAP1 can also contribute. Second, the selective transport of peptides with C-terminal positively charged aa is critically controlled by the amino-terminal region (1-361) on the TAP2 chain, while transport of peptides with C-terminal small polar/hydrophobic aa is determined by residues located within as well as outside the region 1-361. Third, a single point mutation in hTAP2 (374A-->D) resulted in a drastic alteration of the transport pattern. These results indicate that both TAP1 and TAP2 contribute to efficient peptide transport and that single point mutations in hTAP2 are able to alter the peptide transport specificity. This opens the possibility that naturally occurring mutations in one of the hTAP subunits may alter epitope selection in vivo.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 3; ATP-Binding Cassette Transporters; Amino Acid Sequence; Animals; Antigen Presentation; Base Sequence; Biological Transport; Epitopes; Humans; Mice; Molecular Sequence Data; Peptides; Phenotype; Point Mutation; Rats; Rats, Inbred Lew; Species Specificity
PubMed: 8765016
DOI: 10.1002/eji.1830260813 -
The Journal of Pharmacology and... Jul 2006Midodrine is an oral drug for orthostatic hypotension. This drug is almost completely absorbed after oral administration and converted into its active form,... (Comparative Study)
Comparative Study
Midodrine is an oral drug for orthostatic hypotension. This drug is almost completely absorbed after oral administration and converted into its active form, 1-(2',5'-dimethoxyphenyl)-2-aminoethanol) (DMAE), by the cleavage of a glycine residue. The intestinal H+-coupled peptide transporter 1 (PEPT1) transports various peptide-like drugs and has been used as a target molecule for improving the intestinal absorption of poorly absorbed drugs through amino acid modifications. Because midodrine meets these requirements, we examined whether midodrine can be a substrate for PEPT1. The uptake of midodrine, but not DMAE, was markedly increased in PEPT1-expressing oocytes compared with water-injected oocytes. Midodrine uptake by Caco-2 cells was saturable and was inhibited by various PEPT1 substrates. Midodrine absorption from the rat intestine was very rapid and was significantly inhibited by the high-affinity PEPT1 substrate cyclacillin, assessed by the alteration of the area under the blood concentration-time curve for 30 min and the maximal concentration. Some amino acid derivatives of DMAE were transported by PEPT1, and their transport was dependent on the amino acids modified. In contrast to neutral substrates, cationic midodrine was taken up extensively at alkaline pH, and this pH profile was reproduced by a 14-state model of PEPT1, which we recently reported. These findings indicate that PEPT1 can transport midodrine and contributes to the high bioavailability of this drug and that Gly modification of DMAE is desirable for a prodrug of DMAE.
Topics: Amino Acids; Animals; Caco-2 Cells; Dose-Response Relationship, Drug; Female; Humans; Hypotension, Orthostatic; Membrane Transport Proteins; Midodrine; Oocytes; Protein Transport; Rats; Xenopus laevis
PubMed: 16597710
DOI: 10.1124/jpet.106.102830 -
FEBS Letters Jul 1991Protein export in prokaryotes as well as in eukaryotes can be defined as protein transport across the plasma membrane. In both types of organisms there are various... (Review)
Review
Protein export in prokaryotes as well as in eukaryotes can be defined as protein transport across the plasma membrane. In both types of organisms there are various apparently ATP-dependent transport mechanisms which can be distinguished from one another and which show similarities when the prokaryotic mechanism is compared with the respective eukaryotic mechanism. First, one can distinguish between transport mechanisms which involve so-called signal or leader peptides and those which do not. The latter mechanisms seem to employ ATP-dependent transport systems which belong to the family of oligopeptide permeases and multiple drug resistance proteins. Second, in signal or leader peptide-dependent transport one can distinguish between transport mechanisms which involve ribonucleoparticles and those which employ molecular chaperones. Both mechanisms appear to converge at the level of ATP-dependent translocases.
Topics: Animals; Bacterial Proteins; Biological Transport, Active; Carrier Proteins; Cell Membrane; Dogs; Escherichia coli; Fungal Proteins; Membrane Transport Proteins; Models, Biological; Protein Sorting Signals; Proteins; Ribosomal Proteins; Yeasts
PubMed: 1855588
DOI: 10.1016/0014-5793(91)80800-i