Structure and dynamics of IgE-receptor interactions: FcεRI and CD23/FcεRII.
Immunoglobulin E (IgE) is well known for its role in allergic disease, the manifestations of which are mediated through its two Fc receptors, FcεRI and CD23 (FcεRII). IgE and its interactions with these receptors are therefore potential targets for therapeutic intervention, and exciting progress has been made in this direction. Furthermore, recent structural studies of IgE-Fc, the two receptors, and of their complexes, have revealed a remarkable degree of plasticity at the IgE-CD23 interface and an even more remarkable degree of dynamic flexibility within the IgE molecule. Indeed, there is allosteric communication between the two receptor-binding sites, which we now know are located at some distance from each other in IgE-Fc (at opposite ends of the Cε3 domain). The conformational changes associated with FcεRI and CD23 binding to IgE-Fc ensure that their interactions are mutually incompatible, and it may be that this functional imperative has driven IgE to evolve such a dynamic structure. Appreciation of these new structural data has revised our view of IgE structure, shed light on the co-evolution of antibodies and their receptors, and may open up new therapeutic opportunities.
Randall Division of Cell and Molecular Biophysics, King's College London, London, UK.|Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.
Brian J
BJ
Sutton
Randall Division of Cell and Molecular Biophysics, King's College London, London, UK.|Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.
Anna M
AM
Davies
D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D017455:Receptors, IgE / Q000737:chemistry* / Q000378:metabolism*
D017455:Receptors, IgE; D007073:Immunoglobulin E
CD23; Fc receptor; FcεRI; antibody; immunoglobulin E