Structure and mechanism of mammalian ferroportin

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Project Summary: Ferroportin is the only iron exporter in humans. Mutations in ferroportin cause hemochromatosis. Ferrorpotin is regulated by a peptide hormone hepcidin, which is produced in the liver and inhibits the activity of ferrorportin by inducing endocytosis and by direct inhibition of ferroportin activity. The FPN-hepcidin axis is a potential therapeutic target for normalizing iron homeostasis in hemochromatosis. However, very little is known about how ferroportin recognizes and transport iron and how it interacts with hepcidin. In this study, I will combine structural and functional analyses to understand the mechanism of iron transport and inhibition in ferroportin at the atomic resolution.