Structural highlights
FunctionPublication Abstract from PubMedAnti-IgE therapeutics interfere with the ability of IgE to bind to its receptors on effector cells. Here we report the crystal structure of an anti-IgE single-domain antibody in complex with an IgE Fc fragment, revealing how the antibody inhibits interactions between IgE and the two receptors FcepsilonRI and CD23. The epitope overlaps only slightly with the FcepsilonRI-binding site but significantly with the CD23-binding site. Solution scattering studies of the IgE Fc reveal that antibody binding induces a half-bent conformation in between the well-known bent and extended IgE Fc conformations. The antibody acts as functional homolog of CD23 and induces a closed conformation of IgE Fc incompatible with FcepsilonRI binding. Notably the antibody displaces IgE from both CD23 and FcepsilonRI, and abrogates allergen-mediated basophil activation and facilitated allergen binding. The inhibitory mechanism might facilitate strategies for the future development of anti-IgE therapeutics for treatment of allergic diseases. Trapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts FcepsilonRI interaction.,Jabs F, Plum M, Laursen NS, Jensen RK, Molgaard B, Miehe M, Mandolesi M, Rauber MM, Pfutzner W, Jakob T, Mobs C, Andersen GR, Spillner E Nat Commun. 2018 Jan 2;9(1):7. doi: 10.1038/s41467-017-02312-7. PMID:29295972[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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