Structure of the human IgE-Fc C epsilon 3-C epsilon 4 reveals conformational flexibility in the antibody effector domains

IgE antibodies mediate antiparasitic immune responses and the inflammatory reactions of allergy and asthma. We have solved the crystal structure of the human IgE-Fc C epsilon 3-C epsilon 4 domains to 2.3 Angstrom resolution. The structure reveals a large rearrangement of the N-terminal C epsilon 3 domains when compared to related IgG-Fc structures and to the IgE-Fc bound to its high-affinity receptor, Fc epsilon RI. The IgE-Fc adopts a more compact, closed configuration that places the two C epsilon 3 domains in close proximity, decreases the size of the interdomain cavity, and obscures part of the FceRI binding site. IgE-Fc conformational flexibility may be required for interactions with two distinct IgE receptors, and the structure suggests strategies for the design of therapeutic compounds for the treatment of IgE-mediated diseases.