Carbohydrate Recognition In Cellular Function

Contributors to this volume explore the role of carbohydrates in communication between cells of multicellular organisms. Topics covered include the thermodynamics and spatial restrictions of oligosaccharide-protein interactions, the role of carbohydrates in recognition and as components of cell adhesion molecules, and abnormal glycosylation in several disease states.

This book contains contributions from interdisciplinary scientists to collectively address the issue of targeting carbohydrate recognition for the development of novel therapeutic and diagnostic agents. The book covers (1) biological problems involving carbohydrate recognition, (2) structural factors mediating carbohydrate recognition, (3) design and synthesis of lectin mimics that recognize carbohydrate ligands with high specificity and affinity, and (4) modulation of biological and pathological processes through carbohydrate recognition.

In the last decade there has been a great expansion in our knowledge of the existence, nature and functions of mammalian carbohydrate binding proteins. This book covers the structures and postulated functions for the major classes of mammalian carbohydrate binding proteins. These include intracellular lectins involved in diverse functions such as protein synthesis quality control, targetting of lysosomal enzymes and in the secretory pathway. In addition, several chapters are devoted to other major families of lectins that are found at the cell surface or in extracellular fluids which are involved in various recognition functions such as cell-cell interactions in inflammation and recognition of pathogen carbohydrates in host defence.

Sugar chains (glycans) are often attached to proteins and lipids and have multiple roles in the organization and function of all organisms. "Essentials of Glycobiology" describes their biogenesis and function and offers a useful gateway to the understanding of glycans.

In much of biology, the search for understanding the relation between structure and function is now taking place at the macromolecular level. Proteins, nucleic acids, and polysaccharides are macromolecule--polymers formed from families of simpler subunits. Because of their size and complexity, the polymers are capable of both inter- and intramolecular interactions. These interactions confer upon the polymers distinctive three-dimensional shapes. These tertiary configurations, in turn, determine the function of the macromolecule. Computers have become so inextricably involved in empirical studies of three-dimensional macromolecular structure that mathematical modeling, or theory, and experimental approaches are interrelated aspects of a single enterprise.

Glycans represent a major constituency of post-translational modifications that occur on most, if not all, proteins. Whether on mammalian or invertebrate cell surfaces, they exist as sugar chain moieties designed from the exquisite and coordinated activity of cell-specific glycosylation. Some of the more common glycan structures are linked to cell surface polypeptides via an asparagine (N)-linked residue or a serine/threonine (O)-linked residue, along with a notable contingent found linked to ceramides in the lipid bilayer known as glycosphingolipids. These glycans can associate with complementary glycan-binding proteins (GBP) or lectins to mediate and translate this carbohydrate recognition to cell function. In immunity, there is increasing evidence that precise immune cell glycans are recognized by corresponding GBPs in a cell-intrinsic or -extrinsic manner. Unique carbohydrate recognition domains within GBPs are comprised of precisely spaced amino acid functional groups that allow for selective engagement of a particular glycan target. This structure-function relationship is present in immune signaling pathways, whereby glycans and GBPs on the surface of immune cells (and non-immune cells) help control processes such as immune cell activation, recognition of pathogens, suppression and tissue-specific migration. The diversity of glycan structures and glycosylation among individual immune cell subsets is controlled by the expression of genes involved in glycan biosynthesis including glycosyltransferases, glycosidases, glycan-precursor biosynthetic enzymes and nucleotide-sugar transporters. These genes represent more than 3% of the human genome, and cell-specific expression of these genes dictates a cell’s glycan repertoire, ultimately influencing its molecular interactions with GBPs. Altogether, these emerging lines of investigation highlight the regulatory capacity of glycans in immune health and disease, which in turn, pave the way for novel diagnostic, prognostic, and therapeutic strategies.