Towards Defining the Role of Glycans as Hardware in Information Storage and Transfer: Basic Principles, Experimental Approaches and Recent Progress

Abstract

The term ‘code’ in biological information transfer appears to be tightly and hitherto exclusively connected with the genetic code based on nucleotides and translated into functional activities via proteins. However, the recent appreciation of the enormous coding capacity of oligosaccharide chains of natural glycoconjugates has spurred to give heed to a new concept: versatile glycan assembly by the genetically encoded glycosyltransferases endows cells with a probably not yet fully catalogued array of meaningful messages. Enciphered by sugar receptors such as endogenous lectins the information of code words established by a series of covalently linked monosaccharides as letters for example guides correct intra- and intercellular routing of glycoproteins, modulates cell proliferation or migration and mediates cell adhesion. Evidently, the elucidation of the structural frameworks and the recognition strategies within the operation of the sugar code poses a fascinating conundrum. The far-reaching impact of this recognition mode on the level of cells, tissues and organs has fueled vigorous investigations to probe the subtleties of protein-carbohydrate interactions. This review presents information on the necessarily concerted approach using X-ray crystallography, molecular modeling, nuclear magnetic resonance spectroscopy, thermodynamic analysis and engineered ligands and receptors. This part of the treatise is flanked by exemplarily chosen insights made possible by these techniques.

Comparison of uteroplacental glycosylation in the camel (Camelus dromedarius) and alpaca (Lama pacos)

“…These occurrences indicate that there may be an abnormality in the intercellular responses between maternal uterine epithelium and trophoblast, which may implicate glycan-glycan interactions, as these structures are so abundant at the two apposing cell surfaces. Oligosaccharides are capable of possessing an enormous coding capacity that can mediate cell adhesion (Solís et al, 2001). Whyte and Allen (1985) and Jones et al (2000) have suggested that any aberration of this recognition system may cause a failure in blastocyst attachment at implantation.…”

From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans

“…It is 'the most complex known chemical code in a short sequence among all biological oligomers' (Laine, 1997) and by definition predictive of a host of downstream events. They can be triggered by two principal mechanisms: (i) altering protein folding and routing as well as reactivity with ligands or other proteins, and (ii) acting as biochemical signals decoded by lectins (Sharon and Lis, 1997;Reuter and Gabius, 1999;Solís et al, 2001;Gabius et al, 2004;Honke and Taniguchi, 2009). Hereby, the fundamental functional potential of glycans is broadly realized, giving ample reason for the interest to delineate detailed structure-function relationships.…”

Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells

“…Based on their strategic cell surface presentation and malignancy-associated structural variability, glycan chains of cellular glycoconjugates deserve attention in this respect. In fact, in the interplay with endogenous lectins, such cell surface determinants participate in regulating cell adhesion, spreading, motility, and mitotic activity (Gabius, 1987(Gabius, , 1997Raz and Lotan, 1987;Varki, 1993;Hakomori, 1998;Kaltner and Stierstorfer, 1998;Reuter and Gabius, 1999;Nangia-Makker et al, 2000;Solı´s et al, 2001;Gabius et al, 2002;Kilpatrick, 2002). By often being positioned readily accessible at the tips of the branches of N-and mucin-type O-glycans, b-galactosides or derivatives thereof harbor ideal features to serve as docking sites for lectins (Gabius, 2000;Brewer, 2002).…”