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      Structures and functions of invertebrate glycosylation

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          Abstract

          Glycosylation refers to the covalent attachment of sugar residues to a protein or lipid, and the biological importance of this modification has been widely recognized. While glycosylation in mammals is being extensively investigated, lower level animals such as invertebrates have not been adequately interrogated for their glycosylation. The rich diversity of invertebrate species, the increased database of sequenced invertebrate genomes and the time and cost efficiency of raising and experimenting on these species have enabled a handful of the species to become excellent model organisms, which have been successfully used as tools for probing various biologically interesting problems. Investigation on invertebrate glycosylation, especially on model organisms, not only expands the structural and functional knowledgebase, but also can facilitate deeper understanding on the biological functions of glycosylation in higher organisms. Here, we reviewed the research advances in invertebrate glycosylation, including N- and O-glycosylation, glycosphingolipids and glycosaminoglycans. The aspects of glycan biosynthesis, structures and functions are discussed, with a focus on the model organisms Drosophila and Caenorhabditis. Analytical strategies for the glycans and glycoconjugates are also summarized.

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          Most cited references110

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          Intracellular functions of N-linked glycans.

          N-linked oligosaccharides arise when blocks of 14 sugars are added cotranslationally to newly synthesized polypeptides in the endoplasmic reticulum (ER). These glycans are then subjected to extensive modification as the glycoproteins mature and move through the ER via the Golgi complex to their final destinations inside and outside the cell. In the ER and in the early secretory pathway, where the repertoire of oligosaccharide structures is still rather small, the glycans play a pivotal role in protein folding, oligomerization, quality control, sorting, and transport. They are used as universal "tags" that allow specific lectins and modifying enzymes to establish order among the diversity of maturing glycoproteins. In the Golgi complex, the glycans acquire more complex structures and a new set of functions. The division of synthesis and processing between the ER and the Golgi complex represents an evolutionary adaptation that allows efficient exploitation of the potential of oligosaccharides.
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            Glycosylation and the immune system.

            Almost all of the key molecules involved in the innate and adaptive immune response are glycoproteins. In the cellular immune system, specific glycoforms are involved in the folding, quality control, and assembly of peptide-loaded major histocompatibility complex (MHC) antigens and the T cell receptor complex. Although some glycopeptide antigens are presented by the MHC, the generation of peptide antigens from glycoproteins may require enzymatic removal of sugars before the protein can be cleaved. Oligosaccharides attached to glycoproteins in the junction between T cells and antigen-presenting cells help to orient binding faces, provide protease protection, and restrict nonspecific lateral protein-protein interactions. In the humoral immune system, all of the immunoglobulins and most of the complement components are glycosylated. Although a major function for sugars is to contribute to the stability of the proteins to which they are attached, specific glycoforms are involved in recognition events. For example, in rheumatoid arthritis, an autoimmune disease, agalactosylated glycoforms of aggregated immunoglobulin G may induce association with the mannose-binding lectin and contribute to the pathology.
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              Chemical glycobiology.

              Chemical tools have proven indispensable for studies in glycobiology. Synthetic oligosaccharides and glycoconjugates provide materials for correlating structure with function. Synthetic mimics of the complex assemblies found on cell surfaces can modulate cellular interactions and are under development as therapeutic agents. Small molecule inhibitors of carbohydrate biosynthetic and processing enzymes can block the assembly of specific oligosaccharide structures. Inhibitors of carbohydrate recognition and biosynthesis can reveal the biological functions of the carbohydrate epitope and its cognate receptors. Carbohydrate biosynthetic pathways are often amenable to interception with synthetic unnatural substrates. Such metabolic interference can block the expression of oligosaccharides or alter the structures of the sugars presented on cells. Collectively, these chemical approaches are contributing great insight into the myriad biological functions of oligosaccharides.
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                Author and article information

                Journal
                Open Biol
                Open Biol
                RSOB
                royopenbio
                Open Biology
                The Royal Society
                2046-2441
                January 2019
                30 January 2019
                30 January 2019
                : 9
                : 1
                : 180232
                Affiliations
                [1 ]Institute of Life Sciences, Jiangsu University , Zhenjiang 212013, People's Republic of China
                [2 ]School of Food and Biological Engineering, Jiangsu University , Zhenjiang 212013, People's Republic of China
                Author notes
                Author information
                http://orcid.org/0000-0003-4152-0857
                http://orcid.org/0000-0001-5254-2299
                Article
                rsob180232
                10.1098/rsob.180232
                6367135
                30958118
                9c2a3fc8-6b18-492c-90e7-a5742012de88
                © 2019 The Authors.

                Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : 19 November 2018
                : 8 January 2019
                Funding
                Funded by: National Natural Science Foundation of China, http://dx.doi.org/10.13039/501100001809;
                Award ID: 31702186
                Award ID: 31872425
                Funded by: China Postdoctoral Science Foundation;
                Award ID: 2016M601725
                Funded by: Natural Science Foundation of Jiangsu Province, http://dx.doi.org/10.13039/501100004608;
                Award ID: BK20160509
                Categories
                129
                Review
                Review Article
                Custom metadata
                January 2019

                Life sciences
                glycosylation,invertebrate,glycoconjugates,structure and function,glycan profiling
                Life sciences
                glycosylation, invertebrate, glycoconjugates, structure and function, glycan profiling

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