Glycobiology

Glycobiology examines the structures, biosynthesis and functions of carbohydrate chains (glycans) and their conjugates to proteins and lipids. These glycoconjugates populate cell surfaces, secretions and extracellular matrices and modulate protein folding, stability, trafficking, cell–cell recognition, immune modulation and signalling. Unlike DNA and protein synthesis, glycan assembly depends on coordinated action of glycosyltransferases and glycosidases in the endoplasmic reticulum and Golgi apparatus, using nucleotide-sugar donors and lipid-linked oligosaccharide precursors. As a result, a single protein may display dozens of distinct glycoforms at multiple attachment sites. This micro- and macro-heterogeneity underlies the ability of cells to generate highly specific “glyco-codes” that regulate development, host–microbe interactions, inflammation, tumour progression and many other physiological and pathological processes.

Research from Nature Portfolio

Metabolic reprogramming of mannose flux was shown to reshape N-glycan processing on viral glycoproteins and to dampen pathogenic inflammation. By inhibiting phosphomannose isomerase, glycolytic competition with mannose reduced complex-type N-glycans on viral spikes, impaired infectivity and suppressed pro-inflammatory cytokine release, while synergizing with antiviral treatment in vivo.

High-resolution structures of the human GPI transamidase complex bound to substrate and product analogues have unveiled the molecular basis for broad proprotein recognition and catalysis. Autoinhibitory loops prevent unintended activation, and energetically driven conformational changes link substrate binding to precise cleavage-ligation, offering blueprints for correcting inherited GPI-anchor deficiencies.

Advances in intact glycopeptide analysis now permit accurate proteome-scale mapping of site-specific N-glycans. Stepped-energy mass-spectrometry fragmentation, combined with a dedicated search engine and stringent multi-level false-discovery-rate controls, enabled the identification and quantification of thousands of distinct glycans across mammalian tissues, establishing a foundation for systemic glycoproteomic studies.

Glycobiology publication trend

The graph below shows the total number of articles in glycobiology across all publications each year (not limited to Nature Index journals).

Technical terms

Glycosylation: Enzymatic attachment of carbohydrate chains to proteins or lipids, essential for structure and function.

Glycoconjugate: A molecule comprising a glycan covalently linked to a protein (glycoprotein), lipid (glycolipid) or other scaffold.

N-glycan: A glycan attached via an N-glycosidic bond to an asparagine within the consensus sequence Asn-X-Ser/Thr.

O-glycan: A glycan attached via an O-glycosidic bond to serine, threonine or hydroxylated residues such as hydroxylysine.

Glycosyltransferase: An enzyme that transfers a sugar moiety from an activated nucleotide-sugar donor to an acceptor molecule.

Oligosaccharyltransferase (OST): The multi-subunit enzyme complex that transfers preassembled oligosaccharides to nascent proteins in the ER.

Glycoform: A specific molecular variant of a glycoprotein differing in its glycan composition or structure.

Microheterogeneity: Variation in glycan structures at a single glycosylation site, producing multiple glycoforms.

Macroheterogeneity: Variation in the presence or occupancy of glycosylation sites on a protein, yielding forms with different numbers of glycans.

References

1. Glycosylation: mechanisms, biological functions and clinical implications. Signal Transduction and Targeted Therapy (2024).
2. PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness. Nature Communications (2024).
3. Structures of liganded glycosylphosphatidylinositol transamidase illuminate GPI-AP biogenesis. Nature Communications (2023).
4. pGlyco 2.0 enables precision N-glycoproteomics with comprehensive quality control and one-step mass spectrometry for intact glycopeptide identification. Nature Communications (2017).
5. Stereoselective Synthesis of Heavily Hydroxylated Azepane Iminosugars via Osmium-Catalyzed Tethered Aminohydroxylation. Organic Letters (2023).
6. The function of UDP-glycosyltransferases in plants and their possible use in crop protection. Biotechnology Advances (2023).
7. Implications of Glycosylation in Alzheimer’s Disease. Frontiers in Neuroscience (2021).