Cell surface carbohydrates have been demonstrated to be involved in cellular regulatory processes including homeostasis and pathology. Although the structures of many of these carbohydrates have been elucidated, little is known about their molecular recognition properties other than their interactions with glycosylases and lectins. Lectins are proteins that are widely found in plants and animals that bind to specific carbohydrate determinants. Our research includes characterizing the physical properties of lectins and their interactions with cell surface glycans and glycoproteins in order to determine their molecular recognition properties. Biophysical and biochemical tools are used to explore these interactions including nuclear magnetic resonance spectroscopy, isothermal titration microcalorimetry and x-ray crystallography. Our recent work has provided a model of the interactions of lectins with cell surface glycoprotein receptors in cellular homeostasis and pathology including cancer, and the ability of host lectins in innate immunity to recognize differences in the density of the same glycans found on the host and pathogens. This model has recently been applied to the immunosuppressive activity of human tumors that secrete lectins that down regulate the T-cell receptor on invading cytolytic T lymphocytes by lectin-glycan interactions.
Dam, T. K., Gerken, T. A., Cavada, B. S., Nascimento, K. S., Moura, T. R., and Brewer, C. F., Binding studies of α-Ga1NAc specific lectins to the α-Ga1NAc (Tn-antigen) form of porcine submaxillary mucin and its smaller fragments. J. Biol. Chem. 282; 28256 (2007).
Dam, T. K. and Brewer, C. F., Multivalent lectin-carbohydrate interactions: energetics and mechanisms of binding. Adv. Carbohydr. Chem. Biochem. 63; 139 (2010) (invited review).
Dam, T. K. and Brewer, C. F., Lectins as pattern recognition molecules: the effects of epitope density in innate immunity. Glycobiology 20; 270 (2010).
Dam, T. K. and Brewer, C.F., Maintenance of cell surface glycan density by lectin-glycan interactions: a homeostatic and innate immune regulatory mechanism. Glycobiology 20, 1061 (2010) (Glyco-Forum Section).
Haugstad, K.E., Gerken, T. A., Stokke, B. T., Dam, T. K., Brewer, C. F. and Sletmoen, M., Enhanced self-association of mucins possessing the T- and Tn-carbohydrate cancer antigens at the single molecule level. Biomacromolecules 13; 1400 (2012).
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