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| N-linked glycosylation | |
|---|---|
| Name | N-linked glycosylation |
| Organism | Eukaryota, Bacteria, Archaea |
| Associated with | Glycoproteins, Endoplasmic reticulum, Golgi apparatus |
N-linked glycosylation is a co- and post-translational protein modification in which an oligosaccharide is attached to an asparagine residue within a polypeptide, critically influencing cell biology, immunology, and medicine. Discovered through biochemical studies involving Stanley Cohen, Rita Levi-Montalcini, and structural advances at institutes such as the Max Planck Society and Institut Pasteur, it underpins diverse processes studied by researchers at universities including Harvard University, University of Cambridge, and Massachusetts Institute of Technology. The pathway connects molecular machines in the endoplasmic reticulum and Golgi apparatus to systemic phenotypes observed in clinics associated with institutions like the Mayo Clinic and Johns Hopkins Hospital.
N-linked glycosylation attaches a preassembled oligosaccharide to nascent proteins via the enzyme complex oligosaccharyltransferase, with foundational work carried out by teams at Rockefeller University, Columbia University, and the European Molecular Biology Laboratory. It is conserved across eukaryotic lineages studied in model organisms such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster, and has been characterized in prokaryotic systems including Escherichia coli and archaeal species examined at the Max Planck Institute for Marine Microbiology. Clinical and biochemical implications have driven collaborations among centers like UCSF, Stanford University School of Medicine, and Karolinska Institute.
Biosynthesis begins with assembly of a dolichol-linked oligosaccharide on the cytosolic face of the endoplasmic reticulum membrane, a process elucidated by biochemical groups at Scripps Research, Weizmann Institute of Science, and University of Oxford. Key enzymes include glycosyltransferases and glucosidases characterized in work from Yale University, University of Pennsylvania, and University of Michigan, while oligosaccharyltransferase subunits were identified in studies at Cold Spring Harbor Laboratory and Imperial College London. After transfer to the nascent polypeptide, trimming and remodeling occur via ER glucosidases and mannosidases, with subsequent processing in the Golgi apparatus mediated by enzymes studied at ETH Zurich, University of Tokyo, and University of California, Berkeley.
N-linked sites are typically found within the consensus motif Asn-X-Ser/Thr, a rule refined by structural biology groups using crystallography and cryo-electron microscopy at Ludwig Maximilian University of Munich, Rutherford Appleton Laboratory, and European Synchrotron Radiation Facility. Structural studies of glycoproteins by teams at Stanford Synchrotron Radiation Lightsource, Max Planck Institute for Biophysical Chemistry, and The Scripps Research Institute revealed how local sequence context and tertiary folding influence site accessibility, as further explored in collaborations with The Francis Crick Institute and Institut Curie.
N-glycan maturation spans cellular compartments including the ER, ER-Golgi intermediate compartment characterized in studies at EMBL-EBI, and the Golgi cisternae described by cell biologists at John Innes Centre, University of Edinburgh, and Karolinska Institutet. Vesicular trafficking steps involving COPII and COPI machinery have been elucidated by laboratories at European Molecular Biology Laboratory-EBI, University of California, San Diego, and Princeton University, while endocytic routes and lysosomal targeting intersect with glycan-dependent sorting signals analyzed at Cold Spring Harbor Laboratory and University College London.
N-linked glycans modulate protein folding, stability, and trafficking, themes central to research programs at National Institutes of Health, Howard Hughes Medical Institute, and Wellcome Trust. They govern cell–cell recognition processes investigated in immunology groups at Dana-Farber Cancer Institute, Pasteur Institute, and Salk Institute for Biological Studies, and affect receptor function in pathways studied by investigators at Vanderbilt University, Yale School of Medicine, and The Rockefeller University. Glycosylation patterns influence viral entry and immune evasion in studies of pathogens like Human immunodeficiency virus, Influenza A virus, and SARS-CoV-2 performed at centers including Centers for Disease Control and Prevention, World Health Organization, and Walter Reed Army Institute of Research.
ER quality control mechanisms such as the calnexin-calreticulin cycle and ER-associated degradation (ERAD) were mapped by teams at Mount Sinai Hospital, University of Texas Southwestern Medical Center, and McGill University. Regulatory inputs from signaling pathways studied at Massachusetts General Hospital, Johns Hopkins University School of Medicine, and University of California, Los Angeles adjust glycosylation under stress conditions like the unfolded protein response characterized by researchers at Cold Spring Harbor Laboratory and Scripps Research Institute. Glycan processing is also influenced by metabolic enzymes and nucleotide-sugar availability examined at ETH Zurich, University of Bonn, and Seoul National University.
Defects in N-linked glycosylation cause congenital disorders of glycosylation (CDGs) first described through clinical genetics work at University Hospital Basel, Great Ormond Street Hospital, and The Hospital for Sick Children (Toronto). Specific gene mutations in ALG, PMM2, and OST complexes have been mapped by consortia involving Genomics England, 100,000 Genomes Project, and research units at Broad Institute. Aberrant glycosylation is implicated in cancer progression studied at Memorial Sloan Kettering Cancer Center and MD Anderson Cancer Center, in autoimmune conditions investigated at Cleveland Clinic and Mayo Clinic, and in infectious disease susceptibility researched at National Institute of Allergy and Infectious Diseases and Institut Pasteur.
Category:Glycobiology