Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc epsilon RI alpha

The initiation of immunoglobulin-E (IgE)-mediated allergic responses requir es the binding of IgE antibody to its high-affinity receptor, Fc epsilon RI . Crosslinking of Fc epsilon RI initiates an intracellular signal transduct ion cascade that triggers the release of mediators of the allergic response . The interaction of the crystallizable fragment (Fc) of IgE (IgE-Fc) with Fc epsilon RI is a key recognition event of this process and involves the e xtracellular domains of the Fc epsilon RI alpha-chain. To understand the st ructural basis for this interaction, we have solved the crystal structure o f the human IgE-Fc-Fc epsilon RI alpha complex to 3.5-Angstrom resolution. The crystal structure reveals that one receptor binds one dimeric IgE-Fc mo lecule 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 inter action are conserved in other members of the Fc receptor family. The struct ure suggests new approaches to inhibiting the binding of IgE to Fc epsilon RI for the treatment of allergy and asthma.