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

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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

DOI 10.1006/jmbi.1999.3252

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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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Authors: Lebrón, J. A., West, A. P., & Bjorkman, P. J.
Affiliations: California Institute of Technology (US)
ORCID: Lebrón, José A
West, Anthony P
Venue: Journal of Molecular Biology
Publisher: Elsevier BV
Published: 1999-11
Volume: 294
Issue: 1
Pages: 239-245
ISSN: 0022-2836 (ISSN-L)
DOI: 10.1006/jmbi.1999.3252
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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 › Biochemistry › 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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The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor 1 1Edited by I. A. Wilson

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