Molecular function of sugar-binding receptors in cellular recognition events
Specific arrangements of sugars decorate the surfaces of cells and are attached to proteins released from cells into the circulation and other extracellular spaces. These glycans serve as recognition signals that are bound by special receptors. In animals, many of these receptors bind to endogenous carbohydrate structures, forming the basis for cell-cell adhesion and for the selective removal of proteins from circulation. Other receptors bind foreign carbohydrates on the surfaces of potentially pathogenic micro-organisms and form part of the innate, antibody-independent immune system. Many sugar-binding receptors contain related carbohydrate-recognition domains and mutations in some of these proteins are associated with susceptibility to disease.
This research is a joint project with Dr Maureen Taylor, who is also in the Division of Molecular Biosciences. A combination of biochemical, biophysical and molecular biological approaches allows us to understand how carbohydrate-recognition domains work together to provide selective recognition of glycoproteins and cell surfaces. We also seek to determine how such recognition leads to targeting of biological functions such as complement fixation and how genetic variation in sugar-binding receptors causes changes in their molecular properties and hence contributes to human disease. In addition, our knowledge of the structure and function of carbohydrate-recognition domains can be combined with the results of the human and model organism genome projects to identify novel sugar-binding receptors and thus to develop a broader understanding of the biological roles of sugar recognition.
Taylor ME, Drickamer K, Mammalian sugar-binding receptors: known functions and unexplored roles, FEBS Journal, ISSN:1742-464X
et al., 2018, Absence of a human ortholog of rodent Kupffer cell galactose-binding receptor encoded by the CLEC4f gene, Glycobiology, ISSN:0959-6658
et al., 2017, Insights into Interactions of Mycobacteria with the Host Innate Immune System from a Novel Array of Synthetic Mycobacterial Glycans., ACS Chemical Biology, Vol:12, ISSN:1554-8929, Pages:2990-3002
et al., 2017, Mechanism of pathogen recognition by human dectin-2, Journal of Biological Chemistry, Vol:292, ISSN:1083-351X, Pages:13402-13414
et al., 2016, Binding sites for acylated trehalose analogs of glycolipid ligands on an extended carbohydrate-recognition domain of the macrophage receptor mincle, Journal of Biological Chemistry, Vol:291, ISSN:1083-351X, Pages:21222-21233
et al., 2015, A Novel Mechanism for Binding of Galactose-terminatedGlycans by the C-type Carbohydrate Recognition Domain inBlood Dendritic Cell Antigen 2, Journal of Biological Chemistry, Vol:290, ISSN:1083-351X, Pages:16759-16771