Iron/lead transporter

The iron/lead transporter (ILT) family (TC# 2.A.108) is a family of transmembrane proteins within the lysine exporter (LysE) superfamily. The ILT family includes two subfamilies, the iron-transporting (OFeT) family (TC# 2.A.108.1) and the lead-transporting (PbrT) family (TC# 2.A.108.2). A representative list of the proteins belonging to these subfamilies of the ILT family can be found in the Transporter Classification Database.

Iron Transporters

Yeast (Saccharomyces cerevisiae, Candida albicans and Schizosaccharomyces pombe) and other fungi possess high affinity (Km ≈ 0.1 μM) Fe²⁺ uptake systems. These systems depend on cell surface ferroxidases to convert extracellular Fe²⁺ to Fe³⁺ which can then be taken up via either a low-affinity (30 μM) transporter of the FeT family (TC #9.A.9) or a high-affinity OFeT family transporter described here. Two gene products are required for high affinity Fe²⁺ transport, Fet3p which is the oxidase, and Ftr1p which is the permease component.

Fet3p

Fet3p of S. cerevisiae is a multicopper oxidase (636 amino acyl residues) which spans the plasma membrane once (residues 561–584) and has two multicopper oxidase domains (residues 121–141 and 483–494), which possess the ferroxidase activity on the external surface of the plasma membrane. It is a member of the multicopper oxidase family and is therefore homologous to laccase (benzenediol:oxygen oxidoreductase or ligninolytic phenol oxidase), as well as L-ascorbate oxidase, ceruloplasmin and dihydrogeodin oxidase. Its copper binding domain is homologous to that of the PcoA copper binding protein of E. coli.

Ftr1p

Ftr1p is a protein of 404 amino acyl residues which may span the membrane seven times. It exhibits homology with other yeast open reading frames (ORFs) as well as algal, bacterial and archaeal ORFs. The bacterial and archaeal ORFs are highly divergent from the yeast proteins and may therefore serve dissimilar functions. Recently a bacterial iron transporter has been characterized from a marine magnetotactic α-proteobacterium, but errors in the sequence precluded inclusion of this protein in TCDB.

Complex

Simultaneous expression of Fet3p and Ftr1p in yeast is required for proper localization of either protein at the cell surface, suggesting that a complex of the two proteins is formed. Both proteins are coordinately regulated, being expressed at high levels when iron is absent and repressed when iron is replete.

Function

A group translocation reaction in which Fe²⁺ is simultaneously oxidized and transported to Fe³⁺ has been suggested but not demonstrated. Alternatively, Fe²⁺ may be oxidized by Fet3p to Fe³⁺ which may be passed from the Fet3p active site directly to the binding site for Fe³⁺ in Ftr1. Still another possibility is that Fet3p functions only indirectly in transport by allowing membrane insertion, localization or stability of Ftr1p due to the formation of a complex between these two proteins. Regardless of these possibilities, it is not known if a channel or carrier mechanism operates. The nature of the energy coupling process for transport is not established.

A dipartite iron uptake system, FetM (646 aas; 8 TMSs in a 1 + 7 arrangement)/FetP (a periplasmic protein that enhances iron uptake by FetM) (TC# 2.A.108.2.10) has been characterized. FetP binds Cu²⁺ and Mn²⁺ at two different sites, 1.3 Å apart, in this homodimeric protein. The 3-d structure with two Cu²⁺ bound to each of the two subunits revealed different geometries at the two sites. FetMP may be an iron permease with an iron scavenging function, and possibly also an iron reducing function.

Transport Reaction

The generalized transport reaction for the OFeT family is:

(1) Fe³⁺ (out) → Fe³⁺ (in), or

(2) Fe²⁺ (out) + 1/4 O₂ (out) → Fe³⁺ (in) + 1/2 H₂O (out).

Lead Transporters

PbrT

A single protein, PbrT (TC# 2.A.108.2.1), encoded within the lead resistance locus of Ralstonia metallidurans CH34, serves as the prototype for the PbrT family. This protein, when overexpressed, increases sensitivity to Pb²⁺. The protein exhibits a single N-terminal hydrophobic segment (a putative TMS), plus 6 additional putative TMSs in the C-terminal region (residues 420–650) of this 652 aas protein. An N-terminal region (residues 100–218) shows sequence similarity to the C-terminal cytochrome C6 domain of the diheme c-type cytochrome, FixP (A8HZ17), of Azorhizobium caulinodans (30% identity). The C-terminal transmembrane domain (residues 223–619) shows sequence similarity to members of the oxidase-dependent Fe²⁺ transporter, OFeT, family (TC# 2.A.108) including the Ftr1 iron transporter of Saccharomyces cerevisiae (TC# 2.A.108.1.1) (30% identity). Thus, PbrT is related to the OFeT family, both structurally and functionally. An N-terminal domain (residues 100–218 in the R. metallidurans protein) shows similarity to the C-terminal cytochrome C6 domain in the diheme c-type cytochrome, FixP of Azorhizobium caulinodans.

Transport Reaction

The generalized transport reactions catalyzed by members of the PbrT family are:

(1) Pb²⁺ (out) → Pb²⁺ (in), and

(2) Fe²⁺ (out) → Fe²⁺ (in).

See also

• Transport protein
• Solute Carrier Family
• Transporter Classification Database

Further reading

• Cao, J; Woodhall, MR; Alvarez, J; Cartron, ML; Andrews, SC (2007). "EfeUOB (YcdNOB) is a tripartite, acid-induced and CpxAR-regulated, low-pH Fe2+ transporter that is cryptic in Escherichia coli K-12 but functional in E. coli O157:H7". Mol Microbiol. 65 (4): 857–75. doi:10.1111/j.1365-2958.2007.05802.x. PMID 17627767. S2CID 44998004..
• Chan, AC; Doukov, TI; Scofield, M; Tom-Yew, SA; Ramin, AB; Mackichan, JK; Gaynor, EC; Murphy, ME (2010). "Structure and function of P19, a high-affinity iron transporter of the human pathogen Campylobacter jejuni". J Mol Biol. 401 (4): 590–604. doi:10.1016/j.jmb.2010.06.038. PMID 20600116..
• Hložková, K; Suman, J; Strnad, H; Ruml, T; Paces, V; Kotrba, P (2013). "Characterization of pbt genes conferring increased Pb2+ and Cd2+ tolerance upon Achromobacter xylosoxidans A8". Res Microbiol. 164 (10): 1009–18. doi:10.1016/j.resmic.2013.10.002. PMID 24125695..
• Jung, WH; Sham, A; Lian, T; Singh, A; Kosman, DJ; Kronstad, JW (2008). "Iron source preference and regulation of iron uptake in Cryptococcus neoformans". PLOS Pathog. 4 (2): e45. doi:10.1371/journal.ppat.0040045. PMC 2242830. PMID 18282105..
• Mathew, A; Eberl, L; Carlier, AL (2014). "A novel siderophore-independent strategy of iron uptake in the genus Burkholderia". Mol Microbiol. 91 (4): 805–20. doi:10.1111/mmi.12499. PMID 24354890. S2CID 45695964..
• Terzulli, A; Kosman, DJ (2010). "Analysis of the high-affinity iron uptake system at the Chlamydomonas reinhardtii plasma membrane". Eukaryot Cell. 9 (5): 815–26. doi:10.1128/EC.00310-09. PMC 2863958. PMID 20348389..
• VanOrsdel, CE; Bhatt, S; Allen, RJ; Brenner, EP; Hobson, JJ; Jamil, A; Haynes, BM; Genson, AM; Hemm, MR (2013). "The Escherichia coli CydX protein is a member of the CydAB cytochrome bd oxidase complex and is required for cytochrome bd oxidase activity". J Bacteriol. 195 (16): 3640–50. doi:10.1128/JB.00324-13. PMC 3754557. PMID 23749980..
• Ziegler, L; Terzulli, A; Gaur, R; McCarthy, R; Kosman, DJ (2011). "Functional characterization of the ferroxidase, permease high-affinity iron transport complex from Candida albicans". Mol Microbiol. 81 (2): 473–85. doi:10.1111/j.1365-2958.2011.07704.x. PMC 3133879. PMID 21645130..

References

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