title: IgE binds asymmetrically to its B cell receptor CD23.
abstract: The antibody IgE plays a central role in allergic disease mechanisms. Its effector functions are controlled through interactions between the Fc region and two principal cell surface receptors FcεRI and CD23. The interaction with FcεRI is primarily responsible for allergic sensitization and the inflammatory response, while IgE binding to CD23 is involved in the regulation of IgE synthesis and allergen transcytosis. Here we present the crystal structure of a CD23/IgE-Fc complex and conduct isothermal titration calorimetric binding studies. Two lectin-like "head" domains of CD23 bind to IgE-Fc with affinities that differ by more than an order of magnitude, but the crystal structure reveals only one head bound to one of the two identical heavy-chains in the asymmetrically bent IgE-Fc. These results highlight the subtle interplay between receptor binding sites in IgE-Fc and their affinities, the understanding of which may be exploited for therapeutic intervention in allergic disease.
authors.affiliation: Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre and Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester, M1 7DN, U.K.
authors.forename: Balvinder
authors.initials: B
authors.lastname: Dhaliwal
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences &Medicine, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, U.K.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, London, U.K.
authors.forename: Marie O Y
authors.initials: MO
authors.lastname: Pang
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences &Medicine, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, U.K.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, London, U.K.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Keeble
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences &Medicine, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, U.K.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, London, U.K.
authors.forename: Louisa K
authors.initials: LK
authors.lastname: James
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences &Medicine, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, U.K.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, London, U.K.
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Gould
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences &Medicine, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, U.K.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, London, U.K.
authors.forename: James M
authors.initials: JM
authors.lastname: McDonnell
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences &Medicine, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, U.K.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, London, U.K.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Sutton
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences &Medicine, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, U.K.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, London, U.K.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Beavil
mesh_terms: D000485:Allergens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology*; D057900:Transcytosis / Q000276:immunology
chemical_list: D000485:Allergens; D007141:Immunoglobulin Fc Fragments; D017455:Receptors, IgE; D007073:Immunoglobulin E