Crystal Structure of the Ectodomain of Human Transferrin Receptor
Abstract
The transferrin receptor (TfR) undergoes multiple rounds of clathrin-mediated endocytosis and reemergence at the cell surface, importing iron-loaded transferrin (Tf) and recycling apotransferrin after discharge of iron in the endosome. The crystal structure of the dimeric ectodomain of the human TfR, determined here to 3.2 angstroms resolution, reveals a three-domain subunit. One domain closely resembles carboxy- and aminopeptidases, and features of membrane glutamate carboxypeptidase can be deduced from the TfR structure. A model is proposed for Tf binding to the receptor.
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HFE appears to block Tf binding to TfR through direct competition for the same binding site.
“In this manner, HFE appears to block Tf binding to TfR through direct competition for the same binding site (179).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [179]
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- Authors
- Lawrence, C. M., Ray, S., Babyonyshev, M., Galluser, R., Borhani, D. W., & Harrison, S. C.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ray, Sanjoy
- Borhani, David W.
- Harrison, Stephen C.
- Venue
- Science
- Published
- 1999-10-22
- Volume
- 286
- Issue
- 5440
- Pages
- 779-782
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2167563458
- Cited by
- 315
- References
- 38
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 13 · 2023: 13 · 2022: 10 · 2021: 4 · 2020: 15 · 2019: 14 · 2018: 9 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 11
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- transferrin receptor, extracellular domain, crystal structure, clathrin-mediated endocytosis, transferrin binding, iron imports, receptor dimer
- MeSH terms
- Amino Acid Sequence, Animals, Carboxypeptidases, Cell Membrane, Ferric Compounds, Glycosylation, Cricetinae, Humans, Hydrogen-Ion Concentration, Models, Molecular, Molecular Sequence Data, Protein Conformation, Receptors, Transferrin, Transferrin, CHO Cells, Conserved Sequence, Protein Structure, Secondary, Protein Structure, Tertiary, Crystallography, X-Ray, Dimerization
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