The repertoire of glycan determinants in the human glycome

Abstract

The number of glycan determinants that comprise the human glycome is not known. This uncertainty arises from limited knowledge of the total number of distinct glycans and glycan structures in the human glycome, as well as limited information about the glycan determinants recognized by glycan-binding proteins (GBPs), which include lectins, receptors, toxins, microbial adhesins, antibodies, and enzymes. Available evidence indicates that GBP binding sites may accommodate glycan determinants made up of 2 to 6 linear monosaccharides, together with their potential side chains containing other sugars and modifications, such as sulfation, phosphorylation, and acetylation. Glycosaminoglycans, including heparin and heparan sulfate, comprise repeating disaccharide motifs, where a linear sequence of 5 to 6 monosaccharides may be required for recognition. Based on our current knowledge of the composition of the glycome and the size of GBP binding sites, glycoproteins and glycolipids may contain approximately 3000 glycan determinants with an additional approximately 4000 theoretical pentasaccharide sequences in glycosaminoglycans. These numbers provide an achievable target for new chemical and/or enzymatic syntheses, and raise new challenges for defining the total glycome and the determinants recognized by GBPs.

Human Plasma Glycome in Attention-Deficit Hyperactivity Disorder and Autism Spectrum Disorders

“…At least 2000 different glycan determinants have been added to the backbone of mammalian polypeptides (15) and the complexity of the glycoproteome is estimated to be several orders of magnitude greater than for the proteome itself (16). N-glycosylation is essential for multicellular life and its complete absence is embryonically lethal (17).…”

A formal approach to the molecular fuzzy lock-and-key

“…Figure 2 shows another example, a frond of the highly flexible 'glycan kelp bed' that coats the cell surface, and, via binding with lectins, triggers even more complicated logical processes. While proteins are constructed from 20 basic amino acids, the glycan kelp bed is formed from as many as 7,000 glycan determinants, and represents a vastly more complex system for information transmission (Cummings, 2009;Gupta et al, 2010). Figure 3, from Dam et al (2007), illustrates a 'bind-andslide' mechanism by which increasing concentration of a lectin species can induce a phase transition topological change.…”

Automated Motif Discovery from Glycan Array Data

“…Current glycan microarrays, such as the one publicly available from the Consortium for Functional Glycomics (CFG), contain less than a thousand glycans, which is considerably below the estimate of over 7000 glycans/glycan determinants in the human glycomes (Cummings, 2009). Nevertheless, such limited microarrays can provide immense insights into potential ligands recognized by a GBP.…”

“…However, the glycan determinants recognized by individual GBPs are just beginning to be understood (Cummings, 2009), and is a major quest of modern glycomics research. The exploration of GBP interactions with glycans on microarrays of defined glycan structures represents a high-throughput method for exploring glycan-binding specificities (Blixt et al, 2004;Feizi and Chai, 2004;Fukui et al, 2002;Powell et al, 2009;Rillahan and Paulson, 2011;Song et al, 2008Song et al, , 2009Tateno et al, 2008;Willats et al, 2002;Zhi et al, 2006).…”