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The Transferrin Receptor Binding Site on HFE, the Class I MHC-related Protein Mutated in Hereditary Hemochromatosis

Lebrón, José A. and Bjorkman, Pamela J. (1999) The Transferrin Receptor Binding Site on HFE, the Class I MHC-related Protein Mutated in Hereditary Hemochromatosis. Journal of Molecular Biology, 289 (4). pp. 1109-1118. ISSN 0022-2836. doi:10.1006/jmbi.1999.2842. https://resolver.caltech.edu/CaltechAUTHORS:20170405-160301407

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Abstract

HFE is a class I major histocompatibility complex (MHC)-related protein that is mutated in patients with the iron storage disease hereditary hemochromatosis. HFE binds tightly to transferrin receptor (TfR), the receptor that mediates uptake of iron-loaded transferrin. The binding affinities for TfR of HFE mutants, designed using the HFE crystal structure, were measured using biosensor assays. The results allow localization of the TfR binding site on HFE to the C-terminal portion of the α1 domain helix and an adjacent loop, a region distinct from the ligand binding sites on class I MHC and related proteins. A biosensor-derived pH-dependent affinity profile for the HFE-TfR interaction is discussed in terms of HFE's hypothesized role in intracellular trafficking.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1006/jmbi.1999.2842DOIArticle
http://www.sciencedirect.com/science/article/pii/S0022283699928425?via%3DihubPublisherArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 1999 Academic Press. Received 24 February 1999, Revised 19 April 1999, Accepted 23 April 1999. We thank Jennifer Johnson, Sarah Sun and Christina Milburn for assistance in making HFE mutants, Arthur Chirino for help with the Figures, W. Lance Martin and Melanie Bennett for suggestions about HFE mutant design, and John Feder and members of the Bjorkman lab for critical reading of the manuscript. J.A.L. was supported by an NIH/NRSA training grant (#GM07616). This work was supported by the Howard Hughes Medical Institute and a grant from the Arthritis Foundation (P.J.B.).
Funders:
Funding AgencyGrant Number
NIH Predoctoral FellowshipGM07616
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Arthritis FoundationUNSPECIFIED
Subject Keywords:functional epitope; class I MHC homolog; iron overload; pH-dependent affinity; surface plasmon resonance
Issue or Number:4
DOI:10.1006/jmbi.1999.2842
Record Number:CaltechAUTHORS:20170405-160301407
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170405-160301407
Official Citation:José A. Lebrón, Pamela J. Bjorkman, The Transferrin Receptor Binding Site on HFE, the Class I MHC-related Protein Mutated in Hereditary Hemochromatosis, Journal of Molecular Biology, Volume 289, Issue 4, 1999, Pages 1109-1118, ISSN 0022-2836, http://dx.doi.org/10.1006/jmbi.1999.2842. (http://www.sciencedirect.com/science/article/pii/S0022283699928425)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75757
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:06 Apr 2017 16:57
Last Modified:15 Nov 2021 16:36

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