Human protein paucimannosylation: cues from the eukaryotic kingdoms

Area of Science:

• Glycobiology
• Biochemistry
• Molecular Biology

Background:

• Paucimannosidic proteins (PMPs) are glycoproteins with truncated mannose-terminating glycans, found across eukaryotes.
• Human PMPs are under-researched despite their association with disease.
• PMPs exhibit structural heterogeneity and tissue-specific expression in various organisms.

Purpose of the Study:

• To comprehensively review the structures, biosynthesis, and functions of PMPs across eukaryotic kingdoms.
• To synthesize current understanding of paucimannosylation's role in human health and disease.
• To highlight the significance and understudied nature of human PMPs.

Main Methods:

• Literature review of biochemical, glycoanalytical, and biological data on PMPs.
• Comparative analysis of PMP structures and expression in different eukaryotic taxa.
• Examination of PMP biosynthetic pathways, including glycoside hydrolase involvement.

Main Results:

• PMPs display significant structural diversity, including fucosylation and xylosylation, particularly in invertebrates and plants.
• Human PMPs, like M2F glycan on neutrophil proteins, are bioactive and not degradation products.
• PMPs are implicated in innate immunity, tumorigenesis, and cellular differentiation, with extravascular localization.

Conclusions:

• Paucimannosylation is widespread but not universal in eukaryotes.
• Human PMPs are distinct bioactive glycoproteins crucial for essential functions, warranting further research.
• Future research should focus on characterizing species-specific PMPs, their biosynthetic routes, and lectin interactions.