Glycosylation in health and disease

Abstract

The glycom e describes the complete repertoire of glycoconjugates com posed of carbohydrate chains, or glycans, that are covalently linked to lipid or protein molecules. Glycoconjugates are formed through a process called glycosylation and can differ in their glycan sequences, the connections between them and their length. Glycoconjugate synthesis is a dynamic process that depends on the local milieu of enzymes, sugar precursors and organelle structures as well as the cell types involved and cellular signals. Studies of rare genetic disorders that affect glycosylation first highlighted the biological importance of the glycome, and technological advances have improved our understanding of its heterogeneity and complexity. Researchers can now routinely assess how the secreted and cell-surface glycom es reflect overall cellular status in health and disease. In fact, changes in glycosylation can modulate inflammatory responses, enable viral immune escape, promote cancer cell metastasis or regulate apoptosis; the com position of the glycom e also affects kidney function in health and disease. New insights into the structure and function of the glycom e can now be applied to therapy developm ent and could improve our ability tofine-tune im m unological responses and inflammation, optimize the performance of therapeutic antibodies and boost immune responses to cancer. These examples illustrate the potential of the emerging field of 'glycomedicine'.

Site-specific N-glycosylation Characterization of Recombinant SARS-CoV-2 Spike Proteins

“…These results indicate the N-glycan compositions and types on S protein largely attribute to different host cells with the differential processing pathways of glycosylation. We can expect that the native N-glycosylation profile of the SARS-CoV-2 S protein in humans tends to be consistent with that of the recombinant protein expressed in human cells, unless the virus buds off early in the glycosylation processing pathway and produces immature glycans (19,27,35). Intriguingly, the immature N-glycans such as high-mannose are regarded as "non-self" glycans (35, 36).…”

“…Glycosylation of proteins is intricately processed by various enzymes coordinated in the endoplasmic reticulum and Golgi apparatus. The glycan composition and structure decoration at specific sites occurred in a non-templated manner governed by host cells, thus frequently resulting in a heterogeneous glycan occupancy on each glycosite (27).…”

“…However, it remains unknown whether MBL can bind to oligomannose on SARS-CoV-2 S protein to impact the viral spread or initiate complement activation in patients. Glycans also play crucial and multifaceted roles in B cell and T cell differentiation via cell-surface or secreted proteins, including selectins, galectins, and siglecs, which can further connect SARS-CoV-2 to immune response and immune regulation (27). In particular, the complex N-glycans are ligands for galectins, which are able to engage different glycoproteins to regulate immune cell infiltration and activation upon virus infection (33,34).…”

Extraction and Partial Characterization of Lectin from Indonesian Brown Algae Padina australis and Padina minor

“…Glycans are one of the most vital components of a cell (Ajit, 2017). The glycan, components of glycoconjugates, is formed through the glycosylation process and mediates many physiological and pathological functions (Reily, Stewart, Renfrow, & Novak, 2019). Many studies reported that glycosylation is involved in many crucial biological processes, e.g., receptor activation, molecular traff icking and clearance, signal transduction, cell adhesion, endocytosis, and host-pathogen interactions (Hyono, Mazda, Okazaki, Tadokoro, & Ohshima, 2008).…”

“…Many studies reported that glycosylation is involved in many crucial biological processes, e.g., receptor activation, molecular traff icking and clearance, signal transduction, cell adhesion, endocytosis, and host-pathogen interactions (Hyono, Mazda, Okazaki, Tadokoro, & Ohshima, 2008). Glycosylation plays a crucial part in many cellular mechanisms of both health and disease, such as tumor cell formation and metastatic diseases (Cadena, Cushman, & Welsh, 2018;Nardy, Freire-de-lima, Freire-de-lima, & Morrot, 2016), viral immune escape, inflammatory responses, and kidney functions (Reily et al, 2019).…”