Iron must cross biological membranes to reach essential intracellular enzymes. Two proteins in the plasma membrane of yeast - a multicopper oxidase, encoded by the FET3 gene, and a permease, encoded by the FTR1 gene - were shown to mediate high-affinity iron uptake. FET3 expression was required for FTR1 protein to be transported to the plasma membrane. FTRI expression was required for apo-FET3 protein to be loaded with copper and thus acquire oxidase activity. FTR1 protein also played a direct role in iron transport. Mutations in a conserved sequence motif of FTR1 specifically blocked iron transport.
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