Dissecting sialoglycan recognition by Siglecs

Human glycans are often capped by sialic acids, a family of diverse 9-carbon backbone sugars. The prominent location at the glycan terminal ends, positions sialic acids at the nexus of numerous molecular interactions at the cell surface. Sialoglycans are structurally diverse and constitute the ligands for a family of sialic acid-binding proteins called the Siglecs. Siglecs are transmembrane proteins expressed on immune cells and other cell types that transmit activating or inhibitory signals upon binding to a specific sialoglycan ligand. The fine-binding specificities of the fourteen human Siglec family members to distinct sialoglycan structures are beginning to emerge. However, understanding how the underlying protein context in which sialoglycans are embedded contributes to selective binding is in its infancy. We dissect this specific binding context of the human Siglec family to unravel their role in the immune system and inflammatory diseases. Moreover, this research can lead to the development of selective Siglec ligands for therapeutic interventions.