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Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor

Bennett, Melanie J. and Lebrón, José A. and Bjorkman, Pamela J. (2000) Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature, 403 (6765). pp. 46-53. ISSN 0028-0836. https://resolver.caltech.edu/CaltechAUTHORS:20150330-092240629

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Abstract

HFE is related to major histocompatibility complex (MHC) class I proteins and is mutated in the iron-overload disease hereditary haemochromatosis. HFE binds to the transferrin receptor (TfR), a receptor by which cells acquire iron-loaded transferrin. The 2.8 Å crystal structure of a complex between the extracellular portions of HFE and TfR shows two HFE molecules which grasp each side of a twofold symmetric TfR dimer. On a cell membrane containing both proteins, HFE would 'lie down' parallel to the membrane, such that the HFE helices that delineate the counterpart of the MHC peptide-binding groove make extensive contacts with helices in the TfR dimerization domain. The structures of TfR alone and complexed with HFE differ in their domain arrangement and dimer interfaces, providing a mechanism for communicating binding events between TfR chains. The HFE–TfR complex suggests a binding site for transferrin on TfR and sheds light upon the function of HFE in regulating iron homeostasis.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/47417DOIArticle
http://www.nature.com/nature/journal/v403/n6765/abs/403046a0.htmlPublisherArticle
http://rdcu.be/cqVtPublisherFree ReadCube access
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2000 Macmillan Magazines Ltd. Received 27 August 1999; Accepted 21 October 1999. We thank C. M. Lawrence and S. C. Harrison for sharing structural information and coordinates before publication; Z. A. Hamburger for assistance with synchrotron data collection; A. Cohen and M. Soltis for synchrotron support; P. M. Snow and I. Nangiana for expression of TfR; S. Jones for assistance with interface analyses; and A. J. Chirino, C. Enns and J. N. Feder for helpful discussions. M.J.B. was supported by a Cancer Research Institute Postdoctoral fellowship.
Funders:
Funding AgencyGrant Number
Cancer Research Institute Postdoctoral FellowshipUNSPECIFIED
Issue or Number:6765
Record Number:CaltechAUTHORS:20150330-092240629
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150330-092240629
Official Citation:Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor p46-53 Melanie J. Bennett, José A. Lebrón and Pamela J. Bjorkman doi:10.1038/47417
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56206
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:30 Mar 2015 16:46
Last Modified:03 Oct 2019 08:12

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