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Ca2+-dependent structural changes in the B-cell receptor CD23 increase its affinity for human immunoglobulin E.

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Yuan D, Keeble AH, Hibbert RG, Fabiane S, Gould HJ, McDonnell JM, Beavil AJ, Sutton BJ, Dhaliwal B
OpenAccess logo J Biol Chem 288 21667-77 (2013)
Related entries: 4g96, 4g9a, 4gi0, 4gjx, 4gk1, 4gko

Cited: 18 times
EuropePMC logo PMID: 23775083

Abstract

Immunoglobulin E (IgE) antibodies play a fundamental role in allergic disease and are a target for therapeutic intervention. IgE functions principally through two receptors, FcεRI and CD23 (FcεRII). Minute amounts of allergen trigger mast cell or basophil degranulation by cross-linking IgE-bound FcεRI, leading to an inflammatory response. The interaction between IgE and CD23 on B-cells regulates IgE synthesis. CD23 is unique among Ig receptors in that it belongs to the C-type (calcium-dependent) lectin-like superfamily. Although the interaction of CD23 with IgE is carbohydrate-independent, calcium has been reported to increase the affinity for IgE, but the structural basis for this activity has previously been unknown. We have determined the crystal structures of the human lectin-like head domain of CD23 in its Ca(2+)-free and Ca(2+)-bound forms, as well as the crystal structure of the Ca(2+)-bound head domain of CD23 in complex with a subfragment of IgE-Fc consisting of the dimer of Cε3 and Cε4 domains (Fcε3-4). Together with site-directed mutagenesis, the crystal structures of four Ca(2+) ligand mutants, isothermal titration calorimetry, surface plasmon resonance, and stopped-flow analysis, we demonstrate that Ca(2+) binds at the principal and evolutionarily conserved binding site in CD23. Ca(2+) binding drives Pro-250, at the base of an IgE-binding loop (loop 4), from the trans to the cis configuration with a concomitant conformational change and ordering of residues in the loop. These Ca(2+)-induced structural changes in CD23 lead to additional interactions with IgE, a more entropically favorable interaction, and a 30-fold increase in affinity of a single head domain of CD23 for IgE. Taken together, these results suggest that binding of Ca(2+) brings an extra degree of modulation to CD23 function.

Articles - 4gj0 mentioned but not cited (1)

  1. Ca2+-dependent structural changes in the B-cell receptor CD23 increase its affinity for human immunoglobulin E. Yuan D, Keeble AH, Hibbert RG, Fabiane S, Gould HJ, McDonnell JM, Beavil AJ, Sutton BJ, Dhaliwal B. J Biol Chem 288 21667-21677 (2013)


Reviews citing this publication (7)

  1. Structure and dynamics of IgE-receptor interactions: FcεRI and CD23/FcεRII. Sutton BJ, Davies AM. Immunol Rev 268 222-235 (2015)
  2. IgE Antibodies: From Structure to Function and Clinical Translation. Sutton BJ, Davies AM, Bax HJ, Karagiannis SN. Antibodies (Basel) 8 19 (2019)
  3. CD69 is the crucial regulator of intestinal inflammation: a new target molecule for IBD treatment? Radulovic K, Niess JH, Niess JH. J Immunol Res 2015 497056 (2015)
  4. How calcium makes endocytic receptors attractive. Andersen CB, Moestrup SK. Trends Biochem Sci 39 82-90 (2014)
  5. The role of CD23 in the regulation of allergic responses. Engeroff P, Vogel M. Allergy 76 1981-1989 (2021)
  6. 100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology. Pomés A, Chruszcz M, Gustchina A, Minor W, Mueller GA, Pedersen LC, Wlodawer A, Chapman MD. J Allergy Clin Immunol 136 29-37.e10 (2015)
  7. On the complexity of IgE: The role of structural flexibility and glycosylation for binding its receptors. Plattner K, Bachmann MF, Vogel M. Front Allergy 4 1117611 (2023)

Articles citing this publication (10)

  1. Allosteric mechanism of action of the therapeutic anti-IgE antibody omalizumab. Davies AM, Allan EG, Keeble AH, Delgado J, Cossins BP, Mitropoulou AN, Pang MOY, Ceska T, Beavil AJ, Craggs G, Westwood M, Henry AJ, McDonnell JM, Sutton BJ. J Biol Chem 292 9975-9987 (2017)
  2. Structural and Physical Basis for Anti-IgE Therapy. Wright JD, Chu HM, Huang CH, Ma C, Chang TW, Lim C. Sci Rep 5 11581 (2015)
  3. Types and effects of protein variations. Vihinen M. Hum Genet 134 405-421 (2015)
  4. IgE binds asymmetrically to its B cell receptor CD23. Dhaliwal B, Pang MO, Keeble AH, James LK, Gould HJ, McDonnell JM, Sutton BJ, Beavil AJ. Sci Rep 7 45533 (2017)
  5. Structural basis for selective inhibition of immunoglobulin E-receptor interactions by an anti-IgE antibody. Chen JB, Ramadani F, Pang MOY, Beavil RL, Holdom MD, Mitropoulou AN, Beavil AJ, Gould HJ, Chang TW, Sutton BJ, McDonnell JM, Davies AM. Sci Rep 8 11548 (2018)
  6. CD23 is a glycan-binding receptor in some mammalian species. Jégouzo SAF, Feinberg H, Morrison AG, Holder A, May A, Huang Z, Jiang L, Lasanajak Y, Smith DF, Werling D, Drickamer K, Weis WI, Taylor ME. J Biol Chem 294 14845-14859 (2019)
  7. The structure-based cancer-related single amino acid variation prediction. Liu JJ, Yu CS, Wu HW, Chang YJ, Lin CP, Lu CH. Sci Rep 11 13599 (2021)
  8. Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Doré KA, Davies AM, Drinkwater N, Beavil AJ, McDonnell JM, Sutton BJ. Biochim Biophys Acta Proteins Proteom 1865 1336-1347 (2017)
  9. Engineering the Fab fragment of the anti-IgE omalizumab to prevent Fab crystallization and permit IgE-Fc complex crystallization. Mitropoulou AN, Ceska T, Heads JT, Beavil AJ, Henry AJ, McDonnell JM, Sutton BJ, Davies AM. Acta Crystallogr F Struct Biol Commun 76 116-129 (2020)
  10. Reviving lost binding sites: Exploring calcium-binding site transitions between human and murine CD23. Ilkow VF, Davies AM, Dhaliwal B, Beavil AJ, Sutton BJ, McDonnell JM. FEBS Open Bio 11 1827-1840 (2021)


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