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 th e 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 d omains when compared to related IgG-Fc structures and to the IgE-Fc bound t o its high-affinity receptor, Fc epsilon RI. The IgE-Fc adopts a more compa ct, closed configuration that places the two C epsilon 3 domains in close p roximity, decreases the size of the interdomain cavity, and obscures part o f the FceRI binding site. IgE-Fc conformational flexibility may be required for interactions with two distinct IgE receptors, and the structure sugges ts strategies for the design of therapeutic compounds for the treatment of IgE-mediated diseases.