highmannosetype

High-mannose type is a classification used in the study of N-linked glycans, describing glycan structures that retain multiple mannose residues attached to the common core. These glycans are one of the three major types of N-linked glycans, alongside hybrid and complex types, and are distinguished by their relatively simple upper arm structures composed mainly of mannose sugars.

Structural features of high-mannose glycans center on the conserved core, consisting of two N-acetylglucosamine (GlcNAc) residues linked to asparagine, with a trimmed core of three mannose residues. The defining characteristic is the presence of additional mannose units on the linked arms, typically forming Man5GlcNAc2 through Man9GlcNAc2. The exact number and linkage patterns of the terminal mannoses can vary, but the overall composition is rich in mannose and lacks the diverse antennae sugars found in complex glycans.

Biosynthesis and processing occur in the endoplasmic reticulum and early Golgi apparatus. The initial N-glycan assembly yields a Glc3Man9GlcNAc2 precursor; after glucose trimming and proper protein folding, further trimming by glycosidases can generate high-mannose forms. When Golgi enzymes modify glycans, some glycoproteins are processed toward hybrid or complex types; otherwise, high-mannose glycans remain predominant. The production environment can influence the degree of processing.

Function and significance include roles in protein folding and quality control through lectin systems such as calnexin/calreticulin, recognition by mannose-binding receptors, and effects on protein stability and immunogenicity. In pathogens and vaccines, high-mannose glycans can influence immune recognition, while in biotherapeutics they affect pharmacokinetics and immunogenic potential.