The structure and function of HFE.
The iron overload disease hereditary haemochromatosis (HH) occurs in about 1 in 300 Caucasians; the protein mutated in this disorder is termed HFE.(1) HFE is homologous to major histocompatibility complex (MHC) class I proteins, but unlike MHC class I molecules, HFE does not present peptides to T cells.(2) The transferrin receptor (TfR) is a ligand for HFE, and the crystal structure of the HFE-TfR complex has been determined.(3) The many interesting features of this structure illustrate the diverse roles of the MHC fold in nature and clarify how HFE affects TfR function. Whether the interaction between HFE and TfR explains the pathogenesis of HH is not so clear.
Drakesmith
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Institute of Molecular Medicine, Oxford, UK. hdrakes@molbiol.ox.ac.uk
Townsend
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D006680:HLA Antigens / Q000737:chemistry* / Q000502:physiology*; D006432:Hemochromatosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins; D009154:Mutation; D011990:Receptors, Transferrin / Q000378:metabolism
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D007501:Iron