Structural insights into biological roles of protein-glycosaminoglycan interactions

The extracellular environment is largely comprised of complex polysaccharides, which were historically considered inert materials that hydrated the cells and contributed to the structural scaffolds. Recent advances in development of sophisticated analytical techniques have brought about a dramatic transformation in understanding the numerous biological roles of these complex polysaccharides. Glycosaminoglycans (GAGs) are a class of these polysaccharides, which bind to a wide variety of proteins and signaling molecules in the cellular environment and modulate their activity, thus impinging on fundamental biological processes. Despite the importance of GAGs modulating biological functions, there are relatively few examples that demonstrate specificity of GAG-protein interactions, which in turn define the structure-function relationships of these polysaccharides. Focusing on heparin/heparan (HSGAGs) and chondroitin/dermatan sulfate (CSGAGs), this review provides structural insights into the oligosaccharide-protein interactions and discusses some key and challenging aspects of understanding GAG structure-function relationships.