Cited by 182Iron Metabolism and DisordersNeurological diseases and metabolismHemoglobin structure and function

The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor 1 1Edited by I. A. Wilson

Lebrón, José A, West, Anthony P, Bjorkman, Pamela J·1999·Journal of Molecular Biology

Abstract

HFE is a class I major histocompatibility complex (MHC)-related protein that is mutated in patients with the iron overload disease hereditary hemochromatosis. HFE binds to transferrin receptor (TfR), the receptor used by cells to obtain iron in the form of diferric transferrin (Fe-Tf). Previous studies demonstrated that HFE and Fe-Tf can bind simultaneously to TfR to form a ternary complex, and that membrane-bound or soluble HFE binding to cell surface TfR results in a reduction in the affinity of TfR for Fe-Tf. We studied the inhibition by soluble HFE of the interaction between soluble TfR and Fe-Tf using radioactivity-based and biosensor-based assays. The results demonstrate that HFE inhibits the TfR:Fe-Tf interaction by binding at or near the Fe-Tf binding site on TfR, and that the Fe-Tf:TfR:HFE ternary complex consists of one Fe-Tf and one HFE bound to a TfR homodimer.

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Crossref · 10.1006/jmbi.1999.3252

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Authors
Lebrón, J. A., West, A. P., & Bjorkman, P. J.
Affiliations
California Institute of Technology (US)
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
1999-11
Volume
294
Issue
1
Pages
239-245
ISSN
0022-2836 (ISSN-L)
OpenAlex
W2061390170
Cited by
182
References
22
Citations by year
2026: 3 · 2025: 3 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 4 · 2013: 10 · 2012: 5
Type
book review
Language
en
Open access
closed
Locations
  • Journal of Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders
National Institute of General Medical Sciences (T32GM007616, GM07616)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords
HFE gene, transferrin receptor 1, hereditary hemochromatosis, iron overload, transferrin, ternary complex, ligand-receptor interactions, iron absorption
MeSH terms
Hemochromatosis Protein, Binding, Competitive, Ferric Compounds, Hemochromatosis, HLA Antigens, Humans, Membrane Proteins, Protein Binding, Receptors, Transferrin, Recombinant Proteins, Transferrin, Biosensing Techniques, Histocompatibility Antigens Class I

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