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#transferrin receptor

2 public questions tagged with this topic.

Protein Sorting and Trafficking

What happens when the transferrin receptor is mutated and cannot bind Fe³⁺ at acidic pH?

Iron uptake in proliferating cells depends on transferrin receptor mediated endocytosis tightly coupled to endosomal acidification. At extracellular pH 7.4 holo transferrin carrying two ferric ions binds transferrin receptor 1 homodimer with nanomolar affinity, clusters via AP2 clathrin adaptor and internalizes into early endosomes. Vacuolar ATPase acidifies lumen to about pH 5.5, protonation of transferrin histidines and nearby receptor residues induces conformational opening of transferrin lobes, reducing Fe3+ affinity by orders of magnitude and releasing ferric iron while apo transferrin re

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 13: Endocytosis and Transferrin Iron Transport.

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Protein Sorting and Trafficking

During receptor-mediated endocytosis of iron, Fe³⁺ is transported into cells via:

Vertebrates transport ferric iron safely via transferrin family to avoid oxidative Fenton radical damage and precipitation. Hepatocytes secrete apo-transferrin 80 kDa bilobed glycoprotein serum loads two Fe3+ each coordinated synergistically bidentate carbonate anion plus four protein ligands two tyrosines histidine aspartate each lobe producing salmon pink complex termed ferrotransferrin diferric transferrin. Doubly loaded species binds transferrin receptor TfR1 homodimer dissociation constant 1-10 nM neutral pH versus 50-fold lower affinity monoferric negligible apo providing selection iron

Ref: Lodish et al., MCB Figure 14-29: Ferrotransferrin carries Fe3+ for uptake via transferrin receptor.

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