Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms.

ABSTRACT: The serum level of iron in humans is tightly controlled by the action of the hormone hepcidin on the iron efflux transporter ferroportin. Hepcidin regulates iron absorption and recycling by inducing the internalization and degradation of ferroportin¹. Aberrant ferroportin activity can lead to diseases of iron overload, such as haemochromatosis, or iron limitation anaemias². Here we determine cryogenic electron microscopy structures of ferroportin in lipid nanodiscs, both in the apo state and in complex with hepcidin and the iron mimetic cobalt. These structures and accompanying molecular dynamics simulations identify two metal-binding sites within the N and C domains of ferroportin. Hepcidin binds ferroportin in an outward-open conformation and completely occludes the

SUBMITTER: Billesbolle CB 

PROVIDER: S-EPMC7906036 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature