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PDBsum entry 1f2q
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Immune system
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PDB id
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1f2q
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Contents |
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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 human high-Affinity ige receptor.
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Authors
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S.C.Garman,
J.P.Kinet,
T.S.Jardetzky.
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Ref.
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Cell, 1998,
95,
951-961.
[DOI no: ]
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PubMed id
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Abstract
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Allergic responses result from the activation of mast cells by the human
high-affinity IgE receptor. IgE-mediated allergic reactions may develop to a
variety of environmental compounds, but the initiation of a response requires
the binding of IgE to its high-affinity receptor. We have solved the X-ray
crystal structure of the antibody-binding domains of the human IgE receptor at
2.4 A resolution. The structure reveals a highly bent arrangement of
immunoglobulin domains that form an extended convex surface of interaction with
IgE. A prominent loop that confers specificity for IgE molecules extends from
the receptor surface near an unusual arrangement of four exposed tryptophans.
The crystal structure of the IgE receptor provides a foundation for the
development of new therapeutic approaches to allergy treatment.
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Figure 4.
Figure 4. Identification of the Fc  epsilon
RI-Binding Site for IgE(A) Residues of Fc epsilon
RI implicated in binding IgE, shown in three orientations of the
receptor (side and top views). Residues that have been
identified by mutagenesis studies in forming the binding site
for the IgE-Fc are shown in yellow. Two residues that affect Fc
epsilon
RI binding to a mutant IgE-Fc (R334S) are shown in magenta.
Carbohydrate attachment sites for all of the human and nonhuman
receptors in Table 2 are colored gray in the Cα track. Note
that the carbohydrate sites cover a substantial portion of the
FcR surface, but they do not impinge on the binding site region
identified by mutagenesis.(B) A surface representation of the
IgE receptor showing the surface exposure of aromatic residues
in blue. The patch corresponding to the four tryptophans is
indicated. Aromatic residues that form part of the predicted
IgE-binding site are also evident in the D2 C-C′ region.
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Figure 5.
Figure 5. Implications for Fc epsilon
RI Specificity and Its Interaction with IgE(A) Four
surface-exposed tryptophans at the top of the D2 domain that are
implicated in IgE binding.(B) Residues in the D2-FG loop and
D1-E strand that are highly variable in human FcR sequences. The
residues in the D2-FG loop have been directly implicated in IgE
binding (see text). The residues in the D1-E strand and the
D1-A′B loop are located near the top of the D2 domain and
could form part of an extended IgE-binding surface between the
two domains. Note that the carbohydrate attachment sites shown
in Figure 4A are consistent with a continuous Fc-binding surface
spanning the two domains involving these D1 loop regions.(C)
Juxtaposition of Fc epsilon
RI with a model for the intact IgE antibody structure. The IgE
model is derived from the intact IgG1 antibody ([17]). The
insertion of the C epsilon
2 domains in the IgE molecule is indicated by dotted lines. The
Fc epsilon
RI α chain is shown relative to the mast cell membrane near the
top of the C epsilon
3 domains that bind to the receptor.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(1998,
95,
951-961)
copyright 1998.
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