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PDBsum entry 1de4
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Metal transport inhibitor/receptor
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PDB id
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1de4
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Contents |
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272 a.a.
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99 a.a.
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635 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the hereditary haemochromatosis protein hfe complexed with transferrin receptor.
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Authors
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M.J.Bennett,
J.A.Lebrón,
P.J.Bjorkman.
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Ref.
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Nature, 2000,
403,
46-53.
[DOI no: ]
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PubMed id
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Abstract
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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 A 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.
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Figure 1.
Figure 1: Ribbon diagrams of HFE, TfR and HFE-TfR structures.
a, HFE^5 (PDB code 1A6Z). Residues substituted in HH mutations
(Cys 260 and His 41)3 and a cluster of histidines (residues 87,
89, 94 and 123) are highlighted. An arrow indicates the inward
displacement of  1
domain helix as compared with the analogous class I MHC helix.
b, TfR monomer from homodimer structure^15 (made using
coordinates provided by C. M. Lawrence and S. C. Harrison). A,
apical loop (residues 312-328); PL, protease-like loop (residues
469-476); C tail, C-terminal tail (residues 750-760). c, Two
views of the HFE-TfR structure related by a 90° rotation about
the vertical axis. Chain termini nearest the predicted
transmembrane region (C terminus for HFE heavy chain; N terminus
for TfR) are labelled (left). The membrane bilayer is
represented by a grey box (right).
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Figure 2.
Figure 2: The HFE-TfR interface. Cut away views of a TfR
monomer (a) and the HFE platform (b) from the HFE-TfR structure
are shown with regions containing residues that form contacts
highlighted in gold (HFE) and aqua (TfR). Side chains of
residues identified by site-directed mutagenesis to affect
ligand binding are highlighted on TfR in cyan (Fe-Tf binding28)
and on HFE in red (TfR binding12). c, Representation of HFE-TfR
interface showing the three-helix bundle and kinked portion of
the HFE 2
helix. d, TCR footprint (pink box) on the structure of a class I
MHC molecule. Arrows indicate the 'high points' on the 1
and 2
helices (Based on Fig. 5 in ref. 4).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2000,
403,
46-53)
copyright 2000.
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