Molecular Recognition of Blood Group Antigens by Human Galectin-1

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1st EuroCarb Young Researcher (ECYR) Workshop

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Mini symposium: Glycobiology at the LUMC and beyond

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Molecular Recognition of Blood Group Antigens by Human Galectin-1

Sara Bertuzzi 1 , Ana Gimeno 1 , Sandra Delgado 1 , Jesús Jiménez-Barbero 1 , Ana Ardá 1

1 CIC Biogune, Derio, Bizkaia, Spain

The recognition of glycans by lectins are key events in many biological processes. Human Galectin-1 is a β-galactoside binding lectin that has been shown to be implicated in a wide range of biological phenomena, including immune response, immune disorders, inflammation, host-pathogen interactions [1], and cancer progression [2].

The glycan binding partners of hGal-1 share the LacNAc disaccharide motif, where modifications at the terminal Gal residue modulate binding affinities [3]. Opposite to hGal-3 [4], modifications resulting in the blood group ABH antigens (Galα1-3 and Fucα1-2) decrease the binding affinity.

With the aim of understanding the molecular basis of this effect, in this work, we have studied the structural features of the complexes between the ABH blood group antigens and hGal-1, by combining Nuclear Magnetic Resonance (NMR) experiments, Isothermal Titration Calorimetry (ITC), and molecular modeling.

Camby, I; Le Mercier, M.; Lefranc, F.; Kisset, R. Glycobiology, 2006, 16, 137R-157R.

Ito, K.; Stannard, K.; Gabutero, E.; Clark A. M.; Neo, S.-Y.; Onturk, S.; Blanchard, H.; Ralph. S. J. Cancer Metastasis Rev, 2012, 31, 763–767.

Stowell, S. R.; Arthur, C. M.; Mehta, P.; Slanina, K. A.; Blixt, O.; Leffler, H.; Smith, D. F.; Cummings, R. D. J. Biol. Chem., 2008, 283, 10109-10123.

Gimeno, A.; Delgado, S.; Valverde, P.; Bertuzzi, S.; Berbís, M. A.; Echavarren, J.; Lacetera, A.; Martín-Santamaría, S.; Surolia, A.; Cañada, F. J.; Jiménez-Barbero, J.; Ardá, A. Angew Chem. Int. Ed. Engl., 2019, doi: 10.1002/anie.201900723.

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