Exploring Transferrin-Receptor Interactions at the Single-Molecule Level

Interaction between the iron transporter protein transferrin (Tf) and its receptor at the cell surface is fundamental for most living organisms. Tf receptor (TfR) binds iron-loaded Tf (holo-Tf) and transports it to endosomes, where acidic pH favors iron release. Iron-free Tf (apo-Tf) is then brought...

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Bibliographic Details
Published in:Biophysical journal 2008-01, Vol.94 (1), p.230-240
Main Authors: Yersin, Alexandre, Osada, Toshiya, Ikai, Atsushi
Format: Article
Language:English
Subjects:
ABC transporters
Barriers
Binding Sites
Biochemistry
Computer Simulation
Contact
Endosomes
Energy of dissociation
Force measurement
Iron
Mica
Microscopy, Atomic Force - methods
Models, Chemical
Models, Molecular
Molecular biology
Molecules
Protein Binding
Protein Conformation
Protein Interaction Mapping
Receptors
Receptors, Transferrin - chemistry
Receptors, Transferrin - ultrastructure
Spectroscopy, Imaging, Other Techniques
T cell receptors
Transferrin - chemistry
Transferrin - ultrastructure
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Summary:Interaction between the iron transporter protein transferrin (Tf) and its receptor at the cell surface is fundamental for most living organisms. Tf receptor (TfR) binds iron-loaded Tf (holo-Tf) and transports it to endosomes, where acidic pH favors iron release. Iron-free Tf (apo-Tf) is then brought back to the cell surface and dissociates from TfR. Here we investigated the Tf-TfR interaction at the single-molecule level under different conditions encountered during the Tf cycle. An atomic force microscope tip functionalized with holo-Tf or apo-Tf was used to probe TfR. We tested both purified TfR anchored to a mica substrate and in situ TfR at the surface of living cells. Dynamic force measurements showed similar results for TfR on mica or at the cell surface but revealed striking differences between holo-Tf-TfR and apo-Tf-TfR interactions. First, the forces necessary to unbind holo-Tf and TfR are always stronger compared to the apo-Tf–TfR interaction. Second, dissociation of holo-Tf-TfR complex involves overcoming two energy barriers, whereas the apo-Tf-TfR unbinding pathway comprises only one energy barrier. These results agree with a model that proposes differences in the contact points between holo-Tf-TfR and apo-Tf-TfR interactions.
ISSN:0006-3495
1542-0086
DOI:10.1529/biophysj.107.114637