An oligopeptide transport gene from Candida albicans

Lubkowitz, Mark; Hauser, Loren; Breslav, Michael; Naider, Fred; Becker, Jeffrey M.

doi:10.1099/00221287-143-2-387

Cited by 95 publications

(117 citation statements)

References 31 publications

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“…A further example is seen in cosmid Ca49C4 (Fig. 4), which contains a pseudogene related to the C. albicans oligopeptide transporter gene OPT1 (29) and its S. cerevisiae homolog YJL212C. The pseudogene has 98% DNA sequence identity over 2 kb to part of OPT1, but a 0.3-kb internal segment has been inverted relative to OPT1 and other members of this gene family.…”

Section: Resultsmentioning

confidence: 99%

Prevalence of small inversions in yeast gene order evolution

Seoighe

Federspiel

Jones

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

138

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Gene order evolution in two eukaryotes was studied by comparing the Saccharomyces cerevisiae genome sequence to extensive new data from whole-genome shotgun and cosmid sequencing of Candida albicans. Gene order is substantially different between these two yeasts, with only 9% of gene pairs that are adjacent in one species being conserved as adjacent in the other. Inversion of small segments of DNA, less than 10 genes long, has been a major cause of rearrangement, which means that even where a pair of genes has been conserved as adjacent, the transcriptional orientations of the two genes relative to one another are often different. We estimate that about 1,100 single-gene inversions have occurred since the divergence between these species. Other genes that are adjacent in one species are in the same neighborhood in the other, but their precise arrangement has been disrupted, probably by multiple successive multigene inversions. We estimate that gene adjacencies have been broken as frequently by local rearrangements as by chromosomal translocations or long-distance transpositions. A bias toward small inversions has been suggested by other studies on animals and plants and may be general among eukaryotes.

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Section: Resultsmentioning

confidence: 99%

Prevalence of small inversions in yeast gene order evolution

Seoighe

Federspiel

Jones

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

138

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“…Furthermore, Gln-222 was found conserved among different OPT members, whereas Gln-526 was present only in Pgt1 but not in the other functionally characterized oligopeptide transporters. This differential pattern of conservation and effect of mutations of Gln-222 and Gln-526 becomes particularly remarkable as Pgt1, like Hgt1p, is the only other PT member characterized to transport glutathione with high affinity, whereas all the other three PT members, AtOpt4, CaOpt1, and Isp4, have been shown to transport tetrapeptides and pentapeptides but do not transport glutathione (4,7,35,36). Taken together, the results suggest that although both glutamine residues participate in substrate transport, Gln-526 is critical in identifying glutathione as substrate, whereas Gln-222 recognizes a structural feature common to oligopeptides, including glutathione, a modified tripeptide.…”

Section: Discussionmentioning

confidence: 99%

“…These include Pgt1, CaOpt1, Isp4, and AtOpt4. Pgt1 has been recently characterized as a high affinity glutathione transporter from Schizosaccharomyces pombe (4), whereas AtOpt4 from Arabidopsis thaliana, CaOpt1 from Candida albicans, and Isp4 from S. pombe have been shown to specifically mediate uptake of oligopeptides (7,35,36).…”

Section: Conservation Pattern Of Residues Important For Hgt1p Functiomentioning

confidence: 99%

Gln-222 in Transmembrane Domain 4 and Gln-526 in Transmembrane Domain 9 Are Critical for Substrate Recognition in the Yeast High Affinity Glutathione Transporter, Hgt1p

Kaur¹,

Bachhawat

2009

Journal of Biological Chemistry

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Hgt1p, a member of the oligopeptide transporter family, is a high affinity glutathione transporter from the yeast Saccharomyces cerevisiae. We have explored the role of polar or charged residues in the putative transmembrane domains of Hgt1p to obtain insights into the structural features of Hgt1p that govern its substrate specificity. A total of 22 charged and polar residues in the predicted transmembrane domains and other conserved regions were subjected to alanine mutagenesis. Functional characterization of these 22 mutants identified 11 mutants which exhibited significant loss in functional activity. All 11 mutants except T114A had protein expression levels comparable with wild type, and all except E744A were proficient in trafficking to the cell surface. Kinetic analyses revealed differential contributions toward the functional activity of Hgt1p by these residues and identified Asn-124 in transmembrane domain 1 (TMD1), Gln-222 in TMD4, Gln-526 in TMD9, and Glu-544, Arg-554, and Lys-562 in the intracellular loop region 537-568 containing the highly conserved proline-rich motif to be essential for the transport activity of the protein. Furthermore, mutants Q222A and Q526A exhibited a nearly 4-and 8-fold increase in the K m for glutathione. Interestingly, although Gln-222 is widely conserved among other functionally characterized oligopeptide transporter family members including those having a different substrate specificity, Gln-526 is present only in Hgt1p and Pgt1, the only two known high affinity glutathione transporters. These results provide the first insights into the substrate recognition residues of a high affinity glutathione transporter and on residues/helices involved in substrate translocation in the structurally uncharacterized oligopeptide transporter family.Hgt1p or ScOpt1p, a polytopic membrane protein, from the yeast Saccharomyces cerevisiae, was the first high affinity glutathione transporter to be identified in any system (1). Hgt1p belongs to a relatively novel family of transporters, the oligopeptide transporter (OPT) 3 family, that contains a large number of fungal, plant, and prokaryotic members (2). The functional characterizations of a few of the fungal and plants members have demonstrated their ability to transport oligopeptides, glutathione, and metal-secondary amino acid conjugates by harnessing the proton gradient across the plasma membrane (3-7). Furthermore, these studies have also highlighted the physiological significance of this family in assimilation/mobilization of oligopeptides as nutrients in fungi and plants and in maintenance of metal homeostasis in plants. However, the majority of the members are yet uncharacterized and need to be defined with respect to their substrate specificity and physiological role.A complete lack of information on the structural features of the OPT family further limits our understanding of this large, uncharacterized family. Identification of residues or motifs critical for substrate recognition among the functionally characterized members woul...

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“…Bacteria, yeasts and filamentous fungi, as well as specialized cells of plants and animals, express membrane proteins for uptake of amino acids, dipeptides and tripeptides (Payne & Smith, 1994;Becker & Naider, 1995;Hauser et al, 2001;Stacey et al, 2002;Rubio-Aliaga & Daniel, 2002). Transporters that also accept oligopeptides of four or five amino acid residues are known in yeasts and plants (Lubkowitz et al, 1997;Hauser et al, 2001;Stacey et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Aminopeptidases and dipeptidyl-peptidases secreted by the dermatophyte Trichophyton rubrum

et al. 2005

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The nature of secreted aminopeptidases in Trichophyton rubrum was investigated by using a reverse genetic approach. T. rubrum genomic and cDNA libraries were screened with Aspergillus spp. and Saccharomyces cerevisiae aminopeptidase genes as the probes. Two leucine aminopeptidases, ruLap1 and ruLap2, and two dipeptidyl-peptidases, ruDppIV and ruDppV, were characterized and compared to orthologues secreted by Aspergillus fumigatus using a recombinant protein from Pichia pastoris. RuLap1 is a 33 kDa nonglycosylated protein, while ruLap2 is a 58-65 kDa glycoprotein. The hydrolytic activity of ruLap1, ruLap2 and A. fumigatus orthologues showed various preferences for different aminoacyl-7-amido-4-methylcoumarin substrates, and various sensitivities to inhibitors and cations. ruDppIV and ruDppV showed similar activities to A. fumigatus orthologues. In addition to endopeptidases, the four aminopeptidases ruLap1, ruLap2, ruDppIV and ruDppV were produced by T. rubrum in a medium containing keratin as the sole nitrogen source. Synergism between endo-and exopeptidases is likely to be essential for dermatophyte virulence, since these fungi grow only in keratinized tissues.

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An oligopeptide transport gene from Candida albicans

Cited by 95 publications

References 31 publications

Prevalence of small inversions in yeast gene order evolution

Prevalence of small inversions in yeast gene order evolution

Gln-222 in Transmembrane Domain 4 and Gln-526 in Transmembrane Domain 9 Are Critical for Substrate Recognition in the Yeast High Affinity Glutathione Transporter, Hgt1p

Aminopeptidases and dipeptidyl-peptidases secreted by the dermatophyte Trichophyton rubrum

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