PDBsum entry 1f2q

Immune system

PDB id: 1f2q

Contents

Protein chain

167 a.a. *

Ligands

NAG-NAG-MAN ×2

NAG

Waters ×73

* Residue conservation analysis

PDB id:

1f2q

Name:

Immune system

Title:

Crystal structure of the human high-affinity ige receptor

Structure:

High affinity immunoglobulin epsilon receptor alpha- subunit. Chain: a. Fragment: extracellular domain. Synonym: fc-epsilon ri-alpha. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: hi-5.

Resolution:

2.40Å R-factor: 0.226 R-free: 0.254

Authors:

S.C.Garman,J.P.Kinet,T.S.Jardetzky

Key ref:

S.C.Garman et al. (1998). Crystal structure of the human high-affinity IgE receptor. Cell, 95, 951-961. PubMed id: 9875849 DOI: 10.1016/S0092-8674(00)81719-5

Date:

28-May-00 Release date: 08-Jun-00

Protein chain

P12319  (FCERA_HUMAN) -  High affinity immunoglobulin epsilon receptor subunit alpha from Homo sapiens

Seq: 257 a.a.

Struc: 167 a.a.

DOI no: 10.1016/S0092-8674(00)81719-5

Cell 95:951-961 (1998)

PubMed id: 9875849

Crystal structure of the human high-affinity IgE receptor.

S.C.Garman, J.P.Kinet, T.S.Jardetzky.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from Cell Press: Cell (1998, 95, 951-961) copyright 1998.

Figures were selected by an automated process.