Conformational changes in IgE contribute to its uniquely slow dissociation rate from receptor Fc[varepsilon]RI

Among antibody classes, IgE has a uniquely slow dissociation rate from, and high affinity for, its cell surface receptor Fc[varepsilon]RI. We show the structural basis for these key determinants of the ability of IgE to mediate allergic hypersensitivity through the 3.4-Å-resolution crystal structure of human IgE-Fc (consisting of the C[varepsilon]2, C[varepsilon]3 and C[varepsilon]4 domains) bound to the extracellular domains of the Fc[varepsilon]RI α chain. Comparison with the structure of free IgE-Fc (reported here at a resolution of 1.9 Å) shows that the antibody, which has a compact, bent structure before receptor engagement, becomes even more acutely bent in the complex. Thermodynamic analysis indicates that the interaction is entropically driven, which explains how the noncontacting C[varepsilon]2 domains, in place of the flexible hinge region of IgG antibodies, contribute together with the conformational changes to the unique binding properties of IgE. [PUBLICATION ABSTRACT]