Immunoglobulin E and its interactions with receptors FcɛRI and CD23 play a central role in
allergic disease. Omalizumab, a clinically approved therapeutic antibody, inhibits the
interaction between IgE and FcɛRI, preventing mast cell and basophil activation, and blocks
IgE binding to CD23 on B cells and antigen-presenting cells. We solved the crystal structure
of the complex between an omalizumab-derived Fab and IgE-Fc, with one Fab bound to
each Cɛ3 domain. Free IgE-Fc adopts an acutely bent structure, but in the complex it is only …