Determination of structural and functional overlap/divergence of five proto-type galectins by analysis of the growth-regulatory interaction with ganglioside GM1 in silico and in vitro on human neuroblastoma cells.

摘要: The growth-regulatory interplay between ganglioside GM1 on human SK-N-MC neuroblastoma cells and an endogenous lectin provides a telling example for glycan (polysaccharide) functionality. Galectin-1 is the essential link sugar signal intracellular response. emerging intrafamily complexity of galectins raises question defining extent their structural functional overlap/divergence. We address this problem proto-type in system: as ligand, target. Using way galectin-1 interacts with complex natural ligand template, we first defined equivalent positioning distinct substitutions other tested galectins, e.g., Lys63 vs. Leu60/Gln72 galectins-2 -5. As predicted from our silico work, have affinity pentasaccharide GM1. In contrast to solid-phase assays, cell surface presentation did not support binding galectin-5, revealing level regulation. Next, monomeric galectin (CG-14) can impair galectin-1-dependent negative growth control by competitively blocking access shared without acting effector. Thus, quaternary structure efficient means give rise divergence. identification second regulation relevant diagnostic monitoring. It might be exploited therapeutically producing variants tailored interfere activities associated malignant phenotype. Moreover, given strategy comparative computational analysis extended sites has implications rational design galectin-type-specific ligands.