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Galectins-1, -2 and -3 exhibit differential recognition of sialylated glycans and blood group antigens

Author

  • Sean R Stowell
  • Connie M Arthur
  • Padmaja Mehta
  • Kristen A Slanina
  • Ola Blixt
  • Hakon Leffler
  • David F Smith
  • Richard D Cummings

Summary, in English

Human galectins have functionally divergent roles, although most of the members of the galectin family bind weakly to the simple disaccharide lactose (Galss1-4Glc). To assess galectin-glycan interactions in more detail, we explored the binding of several important galectins (Gal-1, Gal-2, and Gal-3) on a glycan microarray containing hundreds of structurally diverse glycans. All three galectins exhibited unique glycan binding characteristics. Only Gal-1 and Gal-2 bound complex-type N-glycans and extended core 1 O-glycans with high affinity, while Gal-2 and Gal-3, but not Gal-1, bound A and B blood group antigens. Gal-2 failed to recognize any sialylated glycans regardless of linkage, whereas Gal-1 and Gal-3 bound a2-3, but not a2-6 sialylated glycans. All galectins showed higher binding to sulfated glycans relative to unsulfated ones. Each galectin exhibited higher binding for glycans with poly-N-acetyllactosamine (PL) sequences (Galss1-4GlcNAc)n when compared to N-acetyllactosamine (Galss1-4GlcNAc) in the microarray. However, only Gal-3 preferred PL when assessed by solution-based surface plasmon resonance. Removal of the terminal galactose residue in PL abrogated its recognition by Gal-1 and Gal-2 while having no substantial effect on Gal-3 recognition, demonstrating that Gal-3 recognizes internal N-acetyllactosamine units. These results provide novel insights into the functional constraints of glycan recognition by each galectin and underscore the basis for differences in biological activity.

Publishing year

2008

Language

English

Pages

10109-10123

Publication/Series

Journal of Biological Chemistry

Volume

283

Issue

15

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Microbiology in the medical area
  • Immunology in the medical area

Status

Published

ISBN/ISSN/Other

  • ISSN: 1083-351X