Analyses of carbohydrate recognition by legume lectins: size of the combining site loops and their primary specificity

Abstract

Recognition of cell-surface carbohydrates by lectins has wide implications in important biological processes. The ability of plant lectins to detect subtle variations in carbohydrate structures found on molecules, cells and organisms have made them a paradigm for protein-carbohydrate recognition. Legume lectins, one of the most well studied family of plant proteins, display a considerable repertoire of carbohydrate specificities owing perhaps to the sequence hypervariability in the loops constituting their combining site. However, lack of a rigorous framework to explain their carbohydrate binding specificities has precluded a rational approach to alter their ligand binding activity in a meaningful manner. This study reports an extensive analysis of sequences and structures of several legume lectins and shows that despite the hypervariability of their combining regions they exhibit within a significant pattern of uniformity. The results show that the size of the binding site loop D is invariant in the Man/Glc specific lectins and is possibly a primary determinant of the monosaccharide specificities of the legume lectins. Analyses of size and sequence variability of loops reveal the existence of a common theme that subserves to define their binding specificities. These results thus provide not only a framework for understanding the molecular basis of carbohydrate recognition by legume lectins but also a rationale for redesign of their ligand binding propensities.