Structure of the Fc fragment of human IgE bound to its high-affinity receptor FcεRIα

• Published in: Nature (London) Vol. 406; no. 6793; pp. 259 - 266
• Main Authors: Garman, Scott C., Wurzburg, Beth A., Tarchevskaya, Svetlana S., Kinet, Jean-Pierre, Jardetzky, Theodore S.
• Format: Journal Article
• Language: English
• Published: 20.07.2000
• Subjects: AFc receptors
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35018500

The initiation of immunoglobulin-E (IgE)-mediated allergic responses requires the binding of IgE antibody to its high-affinity receptor, Fc epsilon RI. Crosslinking of Fc epsilon RI initiates an intracellular signal transduction cascade that triggers the release of mediators of the allergic response. The interaction of the crystallizable fragment (Fc) or IgE (IgE-Fc) with Fc epsilon RI is a key recognition event of this process and involves the extracellular domains of the Fc epsilon RI alpha -chain. To understand the structural basis for this interaction, we have solved the crystal structure of the human IgE-Fc epsilon RI alpha complex to 3.5-angstrom resolution. The crystal structure reveals that one receptor binds one dimeric IgE-Fc molecule asymmetrically through interactions at two sites, each involving one C epsilon 3 domain of the IgE-Fc. The interaction of one receptor with the IgE-Fc blocks the binding of a second receptor, and features of this interaction are conserved in other members of the Fc receptor family. The structure suggests new approaches to inhibiting the binding of IgE to Fc epsilon RI for the treatment of allergy and asthma.