Lectin Cross-Linking Interactions with Multivalent Carbohydrates

Abstract

The present findings provide a molecular basis for a new paradigm of specificity in multivalent carbohydrate-lectin interactions, namely the formation of type 2 homogeneous cross-linked lattices between multivalent carbohydrates and lectins. The present x-ray data demonstrate that the cross-linked complexes formed between a series of structurally related divalent carbohydrates and a single tetravalent lectin (SBA) are distinct and due to crystal packing interactions. These results thus provide a molecular basis for the formation of homogeneous type 2 cross-linked complexes between lectins and multivalent carbohydrates and glycoconjugates.

These findings are also relevant to the observations that lectin-carbohydrate cross-linking interactions are involved in cellular recognition and signal transduction processes. For example, activated human T-cells undergo apoptosis due to binding and cross-linking of specific glycoprotein receptors by galectin-1 (Pace et al., 1999). Confocal microscopy shows that the galectin cross-linked glycoprotein receptors form homogeneous aggregates from a population of previously dispersed molecules on the surface of the cells. The crystal structures of the four SBA/pentasaccharide complexes thus repesent models for lectin-carbohydrate clustering in vivo.

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This work was supported by Grant CA-16054 from the National Cancer Institute, Department of Health, Education and Welfare, and Core Grant P30 CA-13330 from the same agency (C.F.B.). Tel. No. (718) 430-2227.

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The abbreviations used are: SBA, lectin from Glycine max (soybean agglutinin); GalNAc, 2-acetamido-2-deoxy-D-galactopyranose; Gal, D-galactopyranose; Glc, D-glucopyranose; GlcNAc, 2-acetamido-2-deoXY-D-glucopyranose; LacNAc, Galβ(1-4)Glc.