highermannose

Higher-mannose, or high-mannose, refers to a class of N-linked glycans on glycoproteins characterized by a core structure with predominantly mannose residues attached to the common N-glycan core. This contrasts with hybrid and complex N-glycans, which incorporate additional sugars beyond mannose, such as galactose, sialic acid, and fucose.

Structure and range: High-mannose glycans have a core GlcNAc2Man3 with various outer mannose branches, typically ranging from Man5GlcNAc2 to Man9GlcNAc2. They are considered middle-stage products of N-glycosylation, arising when processing in the Golgi is limited or early in the secretory pathway.

Biosynthesis and processing: N-glycosylation begins in the endoplasmic reticulum with en bloc transfer of a preassembled oligosaccharide to nascent polypeptides. ER mannosidases trim the chain to yield high-mannose forms, which may be further processed in the Golgi. Enzymes in the Golgi can remodel high-mannose glycans into hybrid or complex types. Sensitivity to certain exoglycosidases, such as Endo H, is often used to distinguish high-mannose/hybrid from complex glycans.

Biological significance: High-mannose glycans play a role in protein folding and quality control within the ER, and in trafficking and stability of glycoproteins. They are also encountered in innate immune recognition, as some lectins and pathogens specifically bind terminal mannose residues.

Analytical and applied aspects: Endoglycosidases like Endo H and PNGase F are commonly used to analyze N-glycan types. In biotechnology, expression systems (e.g., yeast) often produce high-mannose–rich glycoproteins, which can be remodeled or trimmed for therapeutic use.