The mechanism of iron release from the transferrin-receptor 1 adduct.

Article Details

Citation
Copy to clipboard

Hemadi M, Ha-Duong NT, El Hage Chahine JM

The mechanism of iron release from the transferrin-receptor 1 adduct.

J Mol Biol. 2006 May 12;358(4):1125-36. Epub 2006 Mar 13.

PubMed ID
16564538 [ View in PubMed
]
Abstract

We report the determination in cell-free assays of the mechanism of iron release from the N-lobe and C-lobe of human serum transferrin in interaction with intact transferrin receptor 1 at 4.3< or =pH< or =6.5. Iron is first released from the N-lobe in the tens of milliseconds range and then from the C-lobe in the hundreds of seconds range. In both cases, iron loss is rate-controlled by slow proton transfers, rate constant for the N-lobe k(1)=1.20(+/-0.05)x10(6)M(-1)s(-1) and for the C-lobe k(2)=1.6(+/-0.1)x10(3)M(-1)s(-1). This iron loss is subsequent to a fast proton-driven decarbonation and is followed by two proton gains, (pK(1a))/2=5.28 per proton for the N-lobe and (pK(2a))/2=5.10 per proton for the C-lobe. Under similar experimental conditions, iron loss is about 17-fold faster from the N-lobe and is at least 200-fold faster from the C-lobe when compared to holotransferrin in the absence of receptor 1. After iron release, the apotransferrin-receptor adduct undergoes a slow partial dissociation controlled by a change in the conformation of the receptor; rate constant k(3)=1.7(+/-0.1)x10(-3)s(-1). At endosomic pH, the final equilibrated state is attained in about 1000 s, after which the free apotransferrin, two prototropic species of the acidic form of the receptor and apotransferrin interacting with the receptor coexist simultaneously. However, since recycling of the vesicle containing the receptor to the cell surface takes a few minutes, the major part of transferrin will still be forwarded to the biological fluid in the form of the apotransferrin-receptor protein-protein adduct.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Ferric cationTransferrin receptor protein 1ProteinHumans
Yes
Agonist
Details
Ferrous ascorbateTransferrin receptor protein 1ProteinHumans
Unknown
Not AvailableDetails
Ferrous fumarateTransferrin receptor protein 1ProteinHumans
Unknown
Not AvailableDetails
Ferrous gluconateTransferrin receptor protein 1ProteinHumans
Unknown
Not AvailableDetails
Ferrous glycine sulfateTransferrin receptor protein 1ProteinHumans
Unknown
Not AvailableDetails
Ferrous succinateTransferrin receptor protein 1ProteinHumans
Unknown
Not AvailableDetails
IronTransferrin receptor protein 1ProteinHumans
Unknown
Not AvailableDetails
Tetraferric tricitrate decahydrateTransferrin receptor protein 1ProteinHumans
Yes
Ligand
Details