Structure of the Human IgE-Fc Cε3-Cε4 Reveals Conformational Flexibility in the Antibody Effector Domains

AbstractIgE antibodies mediate antiparasitic immune responses and the inflammatory reactions of allergy and asthma. We have solved the crystal structure of the human IgE-Fc Cε3-Cε4 domains to 2.3 Å resolution. The structure reveals a large rearrangement of the N-terminal Cε3 domains when compared to related IgG-Fc structures and to the IgE-Fc bound to its high-affinity receptor, FcεRI. The IgE-Fc adopts a more compact, closed configuration that places the two Cε3 domains in close proximity, decreases the size of the interdomain cavity, and obscures part of the FcεRI 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