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The crystal structure of IgE Fc reveals an asymmetrically bent conformation

Abstract

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 substantial conformational change involving Cε2 must accompany binding to the mast cell receptor FcεRI. This may be the basis of the exceptionally slow dissociation rate of the IgE-FcεRI complex and, thus, of the ability of IgE to cause persistent allergic sensitization of mast cells.

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Figure 1: Domain structure of IgE Fc.
Figure 2: Asymmetry in the contacts between each of the Cε2 domains and the Cε3 and Cε4 domains.
Figure 3: Electron density map showing the two inter-Cε2 domain disulfide bridges.
Figure 4: Comparison of the Cε2:Cε2 and the Cε4:Cε4 interfaces.
Figure 5: Variation in quaternary structure of the Cε3 and Cε4 domains of IgE Fc.
Figure 6: Modeling of the initial complex formed between IgE Fc and sFcεRIα implies a conformational change upon receptor binding.

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Acknowledgements

We thank the National Asthma Campaign (UK), MRC, BBSRC and The Wellcome Trust for their support and the beamline staff at Brookhaven and Hamburg for their assistance and at the SRS (Daresbury, UK) for preliminary data collection. We also thank M. Sanderson and J. Champness (King's College London) for helpful discussions and T. Rutherford for technical help.

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Correspondence to Brian J. Sutton.

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Wan, T., Beavil, R., Fabiane, S. et al. The crystal structure of IgE Fc reveals an asymmetrically bent conformation. Nat Immunol 3, 681–686 (2002). https://doi.org/10.1038/ni811

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