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Transferrin-mediated cellular iron delivery.

ABSTRACT: Essential to iron homeostasis is the transport of iron by the bilobal protein human serum transferrin (hTF). Each lobe (N- and C-lobe) of hTF forms a deep cleft which binds a single Fe(3+). Iron-bearing hTF in the blood binds tightly to the specific transferrin receptor (TFR), a homodimeric transmembrane protein. After undergoing endocytosis, acidification of the endosome initiates the release of Fe(3+) from hTF in a TFR-mediated process. Iron-free hTF remains tightly bound to the TFR at acidic pH; following recycling back to the cell surface, it is released to sequester more iron. Efficient delivery of iron is critically dependent on hTF/TFR interactions. Therefore, identification of the pH-specific contacts between hTF and the TFR is crucial. Recombinant protein production has enabled deconvolution of this complex system. The studies reviewed herein support a model in which pH-induced interrelated events control receptor-stimulated iron release from each lobe of hTF.

SUBMITTER: Luck AN

PROVIDER: S-EPMC4479283 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Transferrin-mediated cellular iron delivery.

Luck Ashley N AN Mason Anne B AB

Current topics in membranes 20120101

Essential to iron homeostasis is the transport of iron by the bilobal protein human serum transferrin (hTF). Each lobe (N- and C-lobe) of hTF forms a deep cleft which binds a single Fe(3+). Iron-bearing hTF in the blood binds tightly to the specific transferrin receptor (TFR), a homodimeric transmembrane protein. After undergoing endocytosis, acidification of the endosome initiates the release of Fe(3+) from hTF in a TFR-mediated process. Iron-free hTF remains tightly bound to the TFR at acidic ...[more]

PMID: 23046645

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