Siglecs (Sialic acid-binding Immunoglobulin (Ig)-like lectins) constitute a family of transmembrane glycan-binding receptors that decorate immune cells surfaces and are implicated in both innate and adaptive immunity. [1,2,3] These lectins recognize and bind sialic acids containing glycans, which represent a common structural motif exposed on all mammalian cells. Siglecs perform many regulatory roles and are involved in events like cell-cell communication, inhibition or regulation of immune tolerance and host-pathogen interactions. [4,5]
We deeply characterized, at atomic level, the recognition of complex-type N-glycans by human and murine Siglec-2, also known as CD22, a B-cell surface inhibitory protein [1,5,6] able to dampen autoimmune responses against self-antigens.  A combination of different techniques, including advanced NMR approaches [8,9,10,11] (Saturation transfer difference, transferred-NOESY), computational methods [12,13] (Molecular Dynamic, Docking, CORCEMA-ST) and biophysical assays (Surface Plasmon Resonance, Alpha Assay) allowed to achieve key information on the epitope mapping and conformation of complex glycans interacting with human/murine Siglec-2.
Our results may have implication in the design of novel glycomimetics able to modulate the activity of Siglec-2 in autoimmune diseases and various B-cell derived malignancies.
- Macauley, M. S.; Crocker, P. R.; Paulson, J. C. Nat. Rev. Immunol. 2014, 14(10), 653– 666.
- Crocker, P. R.; Paulson, J. C.; Varki, A. Nat. Rev. Immunol. 2007, 7, 255–266.
- Cagnoni, J.; PérezSàez, J. M.; Rabinovich, G. A.; Mariño, K. V. Front. Oncol. 2016, 6, 109.
- Pillai, S.; Netravali, I. A.; Cariappa, A.; Mattoo, H. Annu. Rev. Immunol. 2012, 30, 357–92.
- Müller, J.; Nitschke, L. Nat. Rev. Rheumatol. 2014, 10(7), 422-8.
- Han, S.; Collins, B. E.; Bengtson, P.; Paulson, J. C. Nat. Chem. Biol. 2005, 1, 93–97.
- Crocker, P. R.; Redelinghuys, P. Biochem. Soc. Trans. 2008, 36, 1467–1471.
- Meyer, B.; Peters, T. Angew. Chem. Int. Ed. 2003, 42, 864-890.
- Mayer, M.; Meyer, C. Angew. Chem. Int. Ed. Engl. 1999, 38, 1784.
- Enrìquez-Navas, P. M.; Marradi, M.; Padro, D.; Angulo, J.; Penadés, S. Chem. Eur. J. 2011, 17, 1547-1560.
- Marchetti, R. et al. ChemistryOpen 2016, 5(4), 274–296.
- Morris, G. M. et al. J. Comput. Chem. 2009, 30(16), 2785-2791.
- Jayalakshmi, V.; Krishna, N. R. J. Magn. Reson. 2002, 155(1), 106-18.