Engineering receptor recognition and glycosylation sites to discover their role in the physiology of IgE antibodies.


IgE is the least abundant class of antibodies in the circulation and its normal physiology and homoeostasis are poorly understood despite decades of work focusing on its pathophysiological role in allergy. 

Success in discovering these mechanisms will depend on a solid foundation of robust, carefully engineered and well-characterized tool proteins, the critical prerequisite for subsequent in vivo experiments.  Rational approaches to engineering the receptor binding sites on IgE based on our crystal structures of IgE with its receptors will be combined with screening novel mammalian cell display libraries and deep sequencing of the protein repertoires.

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Heyman B, (2002) IgE-mediated enhancement of antibody responses: the beneficial function of IgE?  Allergy 57: 577–585


Holdom, MD, Davies, AM, Nettleship, JE, Bagby, SC, Dhaliwal, B, Girardi, E, Hunt, J, Gould, HJ, Beavil, AJ, McDonnell, JM, Owens, RJ and Sutton, BJ (2011) Conformational Changes in IgE Contribute to Its Uniquely Slow Dissociation Rate From Receptor FcεRI. Nat Struct Mol Biol 18, 571-576


Borthakur S, Hibbert RG, Pang MO, Yahya N, Bax HJ, Kao MW, Cooper AM, Beavil AJ, Sutton BJ, Gould HJ, McDonnell JM. Mapping of the CD23 binding site on immunoglobulin E (IgE) and allosteric control of the IgE-FcεRI interaction. (2012) J Biol Chem. 287(37):31457-61


Dhaliwal B, Yuan D, Pang MO, Henry AJ, Cain K, Oxbrow A, Fabiane SM, Beavil AJ, McDonnell JM, Gould HJ, Sutton BJ. (2012) Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor FcεRI. Proc Natl Acad Sci. 31;109(31):12686-91.


Drinkwater N, Cossins BP, Keeble AH, Wright M, Cain K, Hailu H, Oxbrow A, Delgado J, Shuttleworth LK, Kao MW, McDonnell JM, Beavil AJ, Henry AJ, Sutton BJ. (2014) Human immunoglobulin E flexes between acutely bent and extended conformations. Nat Struct Mol Biol. 21(4):397-404

Biological Areas:

Structural Biology


Molecules, cells and industrial biotechnology