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Understanding Glycosylation: Structure, Function, and Biomedical Relevance
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Glycosylation in Health and Disease
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Glycosylation is a fundamental cellular process in which complex sugar structures are enzymatically added to proteins and lipids, influencing their folding, stability, and interactions, and playing critical roles in cell communication, adhesion, and immune recognition. The vast diversity of the mammalian glycome and its disruption in various diseases underscore glycosylation’s central importance in both normal physiology and pathology.
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Aberrant glycosylation alters cell surface glycoconjugates in tumors, promoting cancer cell proliferation, invasion, metastasis, angiogenesis, and resistance to therapy by modulating signaling pathways and evading programmed cell death mechanisms.
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Glycosylation of viral proteins, such as the SARS-CoV-2 spike protein, influences viral entry and infectivity by modifying receptor interactions and protease cleavage efficiency at key sites like the furin cleavage region.
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In Alzheimer’s disease, changes in glycosylation of key proteins such as amyloid precursor protein (APP) affect their cellular trafficking and processing, influencing the formation of neurotoxic versus non-toxic amyloid species and potentially modifying disease progression.
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Glycosylation shapes immune responses by modifying receptor function on immune cells, particularly T cells, thereby affecting antigen recognition, activation thresholds, and the discrimination between self and non-self, with implications for autoimmunity and immune regulation.
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Glycosylation is a complex, multi-step process that adds diversity to numerous biological molecules, such as proteins and lipids. By affecting a molecule’s stability and function, these modifications play large roles in normal cellular processes and many diseases.
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GlcNAc (N-Acetylglucosamine): Core sugar in N- and O-glycans; regulates protein function and signaling.
Galactose: Terminal sugar; key in cell recognition and lectin binding.
GalNAc (N-Acetylgalactosamine): Initiates O-glycosylation; common in mucins.
Mannose: Central to N-glycan structure and ER protein quality control.
Sialic Acid: Terminal cap; modulates immune response and cell signaling.
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Lectin Applications in Glycobiology
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Lectins are proteins that bind to glycoconjugates via interactions between the ends of glycan chains and lectin carbohydrate recognition domains. These contacts facilitate communication between cells that have extracellular glycoconjugates and lectins, leading to a variety of cellular events, including immune response activation and the regulation of cell adhesion and migration.
Practically, glycobiologists use lectin binding properties as tools to study glycoconjugates. Because lectins recognize sugar structures, they can distinguish glycans with identical sugar compositions that are structurally different.
A lectin’s affinity for its carbohydrate binding partner varies upon even slight changes to the glycan structure, which makes them specific enough for sensitive laboratory assays, such as histology, flow cytometry, affinity chromatography, enzyme assays, and enzyme-linked immunosorbent assays (ELISAs).
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Glycosylation is the enzymatic conjugation of a sugar with a functional group on a macromolecule, such as a protein or lipid, to form a glycoconjugate. Get started with this 8-page guidebook.
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