2.A.67 The Oligopeptide Transporter (OPT) Family

The OPT family consists of functionally well characterized oligopeptide (3-8 amino acid) transporters. One of the yeast homologues is the sexual differentiation process (ISP4) protein of Schizosaccharomyces pombeS. cerevisiae and S. pombe each possess three paralogues of the OPT family. Two transporters from S. cerevisiae, one from S. pombe, and one from Candida albicans have been functionally characterized, and all are peptide uptake systems. Homologues are also found in plants, bacteria and archaea (Gomolplitinant and Saier, 2011).

The prokaryotic homologues are very distant, being revealed only upon PSI-BLAST iterations, and they are also uncharacterized functionally. Energy coupling probable involves H+ symport. While the full-length yeast proteins are reported to be 700-900 residues long and exhibit 12 putative TMSs, bacterial homologue from H. influenzae is 633 amino acyl residues long and exhibits 15 putative TMSs (Gomolplitinant and Saier, 2011).

Eight opt genes encode putative oligopeptide transporters in Candida albicans (e.g. see OPT1, 2.A.67.1.1), almost all of which are represented by polymorphic alleles. opt 1,2,3Δ triple mutants have a severe growth defect, which was rescued by reintroduction of a single copy of OPT1, OPT2 or OPT3.The various oligopeptide transporters differ in their substrate preferences as shown by the ability of strains expressing specific opt genes to grow on peptides of defined length and sequence. These transporters can take up tri-octa peptides, each one with differing specificities (Reuss and Morschhauser, 2006).

An Fe3+-phytosiderophore uptake system of Zea mays, also known as 'yellow stripe1' (YS1) is encoded by the ys1 gene, the expression of which is increased in both roots and shoots under iron deficient conditions (Curie et al., 2001). When expressed in a mutant yeast lacking its native iron uptake system, it corrects the defect specifically in Fe3+-phytosiderophore media. YS1 has a glutamine-rich N-terminus that might function in Fe3+ binding. It has been shown to be a proton symporter that takes up phytosiderophore- and nicotianamine-chelated metals (Schaaf et al., 2004). Nicotianamine is a structural analogue of phytosiderophores and is also an intracellular metal chelator.

Nine genes (designated YS-like genes 1-9 or YS1-9) in Arabidopsis thaliana encode close homologues of YS1 (Curie et al., 2001). These proteins and nine other distant OPT family homologues are of about the same size (about 600 aas) and exhibit 12-13 putative TMSs. Some of these plant proteins may be more similar to the bacterial and archaeal homologues than to the yeast peptide porters. The plant homologues have been reviewed by Lubkowitz (2006).

The generalized transport reactions thought to be catalyzed by members of the OPT family are:

1) Oligopeptide (out) + nH+ (out) → oligopeptide (in) + nH+ (in).

2) Fe3+-phytosiderophore (out) + nH+ (out) → Fe3+-phytosiderophore (in) + nH+ (in)



This family belongs to the .

 

References:

Aoyama T., Kobayashi T., Takahashi M., Nagasaka S., Usuda K., Kakei Y., Ishimaru Y., Nakanishi H., Mori S. and Nishizawa NK. (2009). OsYSL18 is a rice iron(III)-deoxymugineic acid transporter specifically expressed in reproductive organs and phloem of lamina joints. Plant Mol Biol. 70(6):681-92.

Araki, R., J. Murata, and Y. Murata. (2011). A novel barley yellow stripe 1-like transporter (HvYSL2) localized to the root endodermis transports metal-phytosiderophore complexes. Plant Cell Physiol. 52: 1931-1940.

Bock, K.W., D. Honys, J.M. Ward, S. Padmanaban, E.P. Nawrocki, K.D. Hirschi, D. Twell, and H. Sze. (2006). Integrating membrane transport with male gametophyte development and function through transcriptomics. Plant Physiol. 140: 1151-1168.

Bourbouloux, A., P. Shahi, A. Chakladar, S. Delrot, and A.K. Bachhawat. (2000). Hgt1p, a high affinity glutathione transporter from the yeast Saccharomyces cerevisiae. J. Biol. Chem. 275: 13259-13265.

Cho, K. and D.R. Zusman. (1999). Sporulation timing in Myxococcus xanthus is controlled by the espAB locus. Mol. Microbiol. 34: 714-725.

Curie, C., Z. Panaviene, C. Loulergue, S.L. Dellaporta, J-F Briat, and E.L. Walker. (2001). Maize yellow stripe1 encodes a membrane protein directly involved in Fe(III) uptake. Nature 409: 346-349.

DiDonato, R.J. Jr., L.A. Roberts, T. Sanderson, R.B. Eisley, and E.L. Walker. (2004). Arabidopsis Yellow Stripe-Like2 (YSL2): a metal-regulated gene encoding a plasma membrane transporter of nicotianamine-metal complexes. Plant J. 39(3):403-414.

Dworeck, T., K. Wolf, and M. Zimmermann. (2009). SpOPT1, a member of the oligopeptide family (OPT) of the fission yeast Schizosaccharomyces pombe, is involved in the transport of glutathione through the outer membrane of the cell. Yeast 26: 67-73.

Gomolplitinant, K.M. and M.H. Saier, Jr. (2011). Evolution of the oligopeptide transporter family. J. Membr. Biol. 240: 89-110.

Harada, E., K. Sugase, K. Namba, T. Iwashita, and Y. Murata. (2007). Structural element responsible for the Fe(III)-phytosiderophore specific transport by HvYS1 transporter in barley. FEBS Lett. 581: 4298-4302.

Hauser, M., A.M. Donhardt, D. Barnes, F. Naider, and J.M. Becker. (2000). Enkephalins are transported by a novel eukaryotic peptide uptake system. J. Biol. Chem. 275: 3037-3041.

Hauser, M., V. Narita, A.M. Donhardt, F. Naider, and J.M. Becker. (2001). Multiplicity and regulation of genes encoding peptide transporters in Saccharomyces cerevisiae. Mol. Membr. Biol. 18: 105-112.

Lubkowitz, M. (2006). The OPT family functions in long-distance peptide and metal transport in plants. Genet Eng (N Y) 27: 35-55.

Lubkowitz, M.A., D. Barnes, M. Breslav, A. Burchfield, F. Naider, and J.M. Becker. (1998). Schizosaccharomyces pombe isp4 encodes a transporter representing a novel family of oligopeptide transporters. Mol. Microbiol. 28: 729-741.

Lubkowitz, M.A., L. Hauser, M. Breslav, F. Naider, and J.M. Becker. (1997). An oligopeptide transport gene from Candida albicans. Microbiology 143: 387-396.

Reuss, O., J. Morschhäuser. (2006). A family of oligopeptide transporters is required for growth of Candida albicans on proteins. Mol. Microbiol. 60: 795-812.

Sato, S., H. Suzuki, U. Widyastuti, Y. Hotta, and S. Tabatta. (1994). Identification and characterization of genes induced during sexual differentiation in Schizosaccharomyces pombe. Curr. Genet. 26: 31-37.

Schaaf, G., U. Ludewig, B.E. Erenoglu, S. Mori, T. Kitahara, and N. von Wirén. (2004). ZmYS1 functions as a proton-coupled symporter for phytosiderophore- and nicotianamine-chelated metals. J. Biol. Chem. 279: 9091-9096.

Thakur A. and Bachhawat AK. (2015). Charged/Polar-residue scanning of the hydrophobic face of transmembrane domain 9 of the yeast glutathione transporter, hgt1p, reveals a conformationally critical region for substrate transport. G3 (Bethesda). 5(5):921-9.

Thakur, A. and A.K. Bachhawat. (2013). Mutations in the N-terminal region of the Schizosaccharomyces pombe glutathione transporter pgt1(+) allows functional expression in Saccharomyces cerevisiae. Yeast 30: 45-54.

Thakur, A., J. Kaur, and A.K. Bachhawat. (2008). Pgt1, a glutathione transporter from the fission yeast Schizosaccharomyces pombe. FEMS Yeast Res 8: 916-929.

Wang, J.W., Y. Li, Y.X. Zhang, and T.Y. Chai. (2013). Molecular cloning and characterization of a Brassica juncea yellow stripe-like gene, BjYSL7, whose overexpression increases heavy metal tolerance of tobacco. Plant Cell Rep 32: 651-662.

Waters, B.M. , H.H. Chu, R.J. DiDonato, L.A. Roberts, R.B. Eisley, B. Lahner, D.E. Salt, and E.L. Walker. (2006). Mutations in Arabidopsis Yellow Stripe-Like1 and Yellow Stripe-Like3 Reveal Their Roles in Metal Ion Homeostasis and Loading of Metal Ions in Seeds. Plant Physiol. 141(4):1446-1458.

Yen, M.-R., Y.-H. Tseng, and M.H. Saier, Jr. (2001). Maize Yellow Stripe1, an iron-phytosiderophore uptake transporter, is a member of the oligopeptide transporter (OPT) family. Microbiology 147: 2882-2883.

Zulkifli, M. and A.K. Bachhawat. (2017). Identification of residues critical for proton-coupled glutathione translocation in the yeast glutathione transporter, Hgt1p. Biochem. J. 474: 1807-1821.

Zulkifli, M., S. Yadav, A. Thakur, S. Singla, M. Sharma, and A.K. Bachhawat. (2016). Substrate Specificity and Mapping of Residues Critical for Transport in the High Affinity Glutathione Transporter, Hgt1p. Biochem. J. [Epub: Ahead of Print]

Examples:

TC#NameOrganismal TypeExample
2.A.67.1.1Oligopeptide transporter, OPT1 Yeast OPT1 of Candida albicans
 
2.A.67.1.2Sexual differentiation process, ISP4 protein (tetra peptide transporter) Yeast ISP4 of Schizosaccharomyces pombe
 
2.A.67.1.3The YJL212c gene protein (oligopeptide transporter, Opt1p; transports the mammalian pentapeptide, enkephalin, and the tripeptide, glutathione) Yeast Opt1p (YJL212c) of Saccharomyces cerevisiae
 
2.A.67.1.4

High affinity glutathione uptake porter, Hgt1p or OPT2. TMS 9 plays a role in glutathione recognition (Thakur & Bachhawat et al., 2010; Thakur and Bachhawat 2015). Shows highest affinity for reduced glutathione but also transports oxidized glutathione and glutathione conjugates with lesser affinities (Zulkifli et al. 2016). Residues have been identified that are essential for H+-dependent glutathione uptake (Zulkifli and Bachhawat 2017).

Yeast

Hgt1p of Saccharomyces cerevisiae (Q06593)

 
2.A.67.1.5

The glutathione (tripeptide) uptake transporter, Opt1 or Pgt1 (Dworeck et al., 2009).  Transports γ-Glu-Cys-Gly and Glu-Cys-Gly (Thakur et al., 2008).  Mutations in the N-terminus allow functional expression in S. cerevisiae (Thakur and Bachhawat 2013).

Yeast

Opt1 of Schizosaccharomyces pombe (O14031)

 
2.A.67.1.6

Tetra or penta oligopeptide uptake transporter OPT9 (highly expressed in microspores and bipolar pollen; Bock et al., 2006)

Plants

OPT9 of Arabidopsis thaliana (Q9FJD2)

 
Examples:

TC#NameOrganismal TypeExample
2.A.67.2.1'Yellow Stripe1' (YS1) Fe3+-phyto siderophore:H+ symporter. It takes up various metal cations (Fe3+, Zn2+, Cu2+, Ni2+, Mn2+ and Cd2+ when complexed with phytosiderophores, and Ni2+, Fe2+ and Fe3+ when complexed with nicotinamine) (Curie et al., 2001; Schaaf et al., 2004)Plants YS1 of Zea mays
 
2.A.67.2.10

Ferric (Fe3+)-phytosiderophore uptake mediator (Yellow stripe like transporter) of 600 aas and 12 TMSs. The outer membrane loop between the sixth and seventh transmembrane regions is essential for substrate specificity. A synthetic peptide corresponding to the loop of HvYS1 forms an alpha-helix in solution, whereas that of the corn orthologue, ZmYS1, is flexible. Harada et al. 2007 proposed that this structural difference determines the narrow substrate specificity of HvYS1 compared to that of ZmYS1 which is of broad specificity.

HvYS1 of Hordeum vulgare (Barley)

 
2.A.67.2.2The probable metal (iron, copper, and zinc) nicotinamide transporter, YSL1 (Waters et al., 2006) (57% identity with YS1).PlantsYSL1 of Arabidopsis thaliana (Q6R3L0)
 
2.A.67.2.3The metal (iron and copper)-nicotinamide transporter, YSL2 (mediates lateral movement of metals in the vasculature; DiDonato et al., 2004) (62% identity with YS1).PlantsYSL2 of Arabidopsis thaliana (Q6R3K9)
 
2.A.67.2.4The probable metal (iron, copper, and zinc)-nicotinamide transporter, YSL3; functionally redundant with YSL1 (Waters et al., 2006).PlantsYSL3 of Arabidopsis thaliana (Q2EF88)
 
2.A.67.2.5The rice iron(III)-deoxymugineic acid transporter, YSL18 (specifically expressed in reproductive organs and phloem of lamina joints) (Aoyama et al., 2009).

Plants

YSL18 of Oryza sativa (Q941V3)

 
2.A.67.2.6OPT family member

Slime mold

OPT family homologue of Dictyostelium discoideum (Q54EF1)

 
2.A.67.2.7Putative oligopeptide transporter YGL114WFungiYGL114W of Saccharomyces cerevisiae
 
2.A.67.2.8

The metal-phytosiderophore complex transporter, HvYSL2 (Araki et al. 2011).

Plants

HvYSL2 of Hordeum vulgare

 
2.A.67.2.9

Yellow stripe-like 7 protein, YSL7; expression gives rise to heavy metal tolerance in Brassica juncea (Wang et al. 2013).

Plants

YSL7 in Arabidopsis thaliana

 
Examples:

TC#NameOrganismal TypeExample
2.A.67.3.1Early sporulation protein, EspB (temporal control protein) Bacteria EspB of Myxococcus xanthus
 
Examples:

TC#NameOrganismal TypeExample
2.A.67.4.1Orf HI0561/560 Bacteria Orf of Haemophilus influenzae
 
2.A.67.4.2OPT family member

Archaea

OPT family member from Pyrococcus horikoshii (O58099)

 
2.A.67.4.3

OPT family member

Bacteria

OPT protein of Caulobacter crescentus (Q9A523)

 
Examples:

TC#NameOrganismal TypeExample
2.A.67.5.1

Putative oligopeptide transporter

Proteobacteria

Putative oligopeptide transporter of Myxococcus xanthus