The crystal structure of IgE Fc reveals an asymmetrically bent conformation

@article{Wan2002TheCS,
  title={The crystal structure of IgE Fc reveals an asymmetrically bent conformation},
  author={Tommy Wan and Rebecca L. Beavil and Stella Maris Fabiane and Andrew J Beavil and Maninder K. Sohi and M B Keown and Robert J. Young and Alistair J Henry and Raymond J. Owens and Hannah J. Gould and Brian J. Sutton},
  journal={Nature Immunology},
  year={2002},
  volume={3},
  pages={681-686}
}
The distinguishing structural feature of immunoglobulin E (IgE), the antibody responsible for allergic hypersensitivity, is the Cε2 domain pair that replaces the hinge region of IgG. The crystal structure of the IgE Fc (constant fragment) at a 2.6-Å resolution has revealed these domains. They display a distinctive, disulfide-linked Ig domain interface and are folded back asymmetrically onto the Cε3 and Cε4 domains, which causes an acute bend in the IgE molecule. The structure implies that a… Expand

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References

SHOWING 1-10 OF 64 REFERENCES
Structure of the Human IgE-Fc Cε3-Cε4 Reveals Conformational Flexibility in the Antibody Effector Domains
TLDR
IgE-Fc conformational flexibility may be required for interactions with two distinct IgE receptors, and the structure suggests strategies for the design of therapeutic compounds for the treatment of IgE-mediated diseases. Expand
Crystal Structure of the Human High-Affinity IgE Receptor
TLDR
The crystal structure of the IgE receptor provides a foundation for the development of new therapeutic approaches to allergy treatment and reveals a highly bent arrangement of immunoglobulin domains that form an extended convex surface of interaction with IgE. Expand
The structure of the IgE Cɛ2 domain and its role in stabilizing the complex with its high-affinity receptor FcɛRIα
The stability of the complex between IgE and its high-affinity receptor, FcɛRI, on mast cells is a critical factor in the allergic response. The long half-life of the complex of IgE bound to thisExpand
Structure of the Fc fragment of human IgE bound to its high-affinity receptor FcεRIα
The initiation of immunoglobulin-E (IgE)-mediated allergic responses requires the binding of IgE antibody to its high-affinity receptor, FcεRI. Crosslinking of FcεRI initiates an intracellular signalExpand
Basis of the 1:1 stoichiometry of the high affinity receptor FcεRI-IgE complex
Abstract A soluble fragment of the high-affinity IgE receptor FcεRI α-chain (sFcεRIα) binds to the Fc fragment of IgE (IgE-Fc) as a 1:1 complex. IgE-Fc consists of a dimer of the Cε2, Cε3 and Cε4Expand
The analysis of the human high affinity IgE receptor Fc epsilon Ri alpha from multiple crystal forms.
TLDR
The results of this study point to new directions for the design of molecules to inhibit the interaction of Fc epsilon RI alpha with its natural ligand and thus to prevent a primary step in the allergic response. Expand
A Conformational Rearrangement upon Binding of IgE to Its High Affinity Receptor*
TLDR
Binding experiments show that when IgE interacts with α-t there is a 15-26% decrease of the negative ellipticity at 217 nm, which indicates that upon binding, a major conformational rearrangement must occur on IgE. Expand
Interaction of Human IgE with Fc Epsilon RI Alpha Exposes Hidden Epitopes on IgE
TLDR
The hypothesis of a conformational change within IgE Cε3 upon receptor binding is supported by showing that monoclonal antibodies raised against recombinant C ε3 differently recognize soluble and receptor–bound IgE. Expand
The Structure of a Human Type III Fcγ Receptor in Complex with Fc*
Fcγ receptors mediate antibody-dependent inflammatory responses and cytotoxicity as well as certain autoimmune dysfunctions. Here we report the crystal structure of a human Fc receptor (FcγRIIIB) inExpand
Identification of contact residues in the IgE binding site of human FcepsilonRIalpha.
TLDR
These results, together with those from site-directed mutagenesis on fragments of IgE presented in the accompanying paper, define the contact surfaces in the IgE:sFcepsilonRIalpha complex. Expand
...
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2
3
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5
...