Family 9.A.10 - The Low Affinity Fe2+ Transporter Family       

Family ID: 53382

Yeast (Saccharomyces cerevisiae, Candida albicans and Schizosaccharomyces pombe) possess high affinity (Km = 0.1 µM) Fe2+ uptake systems. S. cerevisiaehas two homologues. These systems depend on a cell surface ferrireductase to convert extracellular Fe3+ to Fe2+ which can then be taken up either via a low affinity (30 µM) transporter of the FeT family (TC #9.A.9) or the high affinity OFeT family transporters described here. Two gene products are required for high affinity Fe2+ transport, Fet3p which is an oxidase, and Ftr1p which is believed to be the permease component. Fet3p 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 ferrioxidase 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 is a protein of 404 amino acyl residues which may span the membrane six times. It exhibits homology with other yeast ORFs as well as bacterial (e.g., E. coli, Bacillus subtilis, Synechocystis) and archaeal (e.g., Aeropyrum pernix and Archaeoglobus fulgidus) ORFs, all of unknown function. The bacterial and archaeal ORFs are highly divergent from the yeast proteins and may therefore serve dissimilar functions.

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 Fe is absent and repressed when Fe is replete.

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, the nature of the energy coupling process for transport (e.g., pmf-coupling or electron flow coupling) via Ftr1 has not been examined.