Harnessing glycomics technologies: Integrating structure with function for glycan characterization

Abstract

Glycans, or complex carbohydrates, are a ubiquitous class of biological molecules which impinge on a variety of physiological processes ranging from signal transduction to tissue development and microbial pathogenesis. In comparison to DNA and proteins, glycans present unique challenges to the study of their structure and function owing to their complex and heterogeneous structures and the dominant role played by multivalency in their sequence-specific biological interactions. Arising from these challenges, there is a need to integrate information from multiple complementary methods to decode structure-function relationships. Focusing on acidic glycans, we describe here key glycomics technologies for characterizing their structural attributes, including linkage, modifications, and topology, as well as for elucidating their role in biological processes. Two cases studies, one involving sialylated branched glycans and the other sulfated glycosaminoglycans, are used to highlight how integration of orthogonal information from diverse datasets enables rapid convergence of glycan characterization for development of robust structure-function relationships.

Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential

“…Variations in the local concentration and the charge of large immobile anionic species, including intracellular polyglutamylated neuronal microtubules that are negatively charged at intracellular pH [56,57], as well as the dense and entirely post-translationally sulfated glycosaminoglycans of the ECM [54,58,59] will create opposing Gibbs-Donnan effects [60] that stabilize the intra- and extracellular Cl − microdomains independently of secondarily active transport [25] (Fig. 2).…”

“…Glycoproteins (see Glossary) that comprise the ECM could offset much of the Gibbs-Donnan effects of the intracellular macromolecular anions and balance the Gibbs-Donnan forces. The ECM glycoproteins contain long, starch-like strings of glycosaminoglycans (GAG, see Glossary) [54,58,59]. Each disaccharide moiety of the GAG chains can contain 0 to 4 sulfate groups providing the capacity for very high negative charge density.…”

Application of helium ion microscopy to nanostructured polymer materials

“…Polysaccharides are found throughout the biosphere, alone and also conjugated to other biopolymers such as proteins, in the form of glycoproteins, or to lipids in the form of glycolipids [140,141]. In comparison to nucleic acids and proteins, carbohydrates have larger capacity of complexity through the presence of numerous chiral centers within the sugar/ monosacchride subunits, the greater possible combinations of glycosidic linkages between different carbons within the sugar subunits resulting in branching, and to modifications to individual sugar subunits such as acetylation, methylation, oxidation, and sulfation [139,142]. Given this extraordinary potential diversity, the extent of structural diversity of polysaccharides is just being explored.…”

Surface Glycosylation Profiles of Urine Extracellular Vesicles

“…Precise structural analysis of cell and protein-bound carbohydrates remains a technically challenging field and strategies which employ affinity agents represent a valuable alternative approach for rapidly profiling glycosylation [31], [32]. Lectins are non-antibody, carbohydrate-binding proteins which have affinity for particular carbohydrate components commonly found on the surface of mammalian cells and vesicles derived from them [33].…”