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Taxonomic group: protista / Euglenozoa (Phylum: Euglenozoa)
Host organism: Homo sapiens
Associated disease: Chagas disease [ICD11: 1F53

, ICD11: XN56V

]; infection due to Trypanosoma cruzi [ICD11: XN56V

]; infection due to Trypanosoma brucei [ICD11: XN0C1

]; infection due to Leishmania [ICD11: XN8JE

]

NCBI PubMed ID: 31410980
Publication DOI: 10.1111/brv.12548
Journal NLM ID: 0414576
Publisher: London, Cambridge University Press
Correspondence: morten.andersen

mq.edu.au
Institutions: Department of Molecular Sciences, Macquarie University, Sydney, New South Wales, 2109, Australia, Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore

Paucimannosidic proteins (PMPs) are bioactive glycoproteins carrying truncated α- or β-mannosyl-terminating asparagine (N)-linked glycans widely reported across the eukaryotic domain. Our understanding of human PMPs remains limited, despite findings documenting their existence and association with human disease glycobiology. This review comprehensively surveys the structures, biosynthetic routes and functions of PMPs across the eukaryotic kingdoms with the aim of synthesising an improved understanding on the role of protein paucimannosylation in human health and diseases. Convincing biochemical, glycoanalytical and biological data detail a vast structural heterogeneity and fascinating tissue- and subcellular-specific expression of PMPs within invertebrates and plants, often comprising multi-α1,3/6-fucosylation and β1,2-xylosylation amongst other glycan modifications and non-glycan substitutions e.g. O-methylation. Vertebrates and protists express less-heterogeneous PMPs typically only comprising variable core fucosylation of bi- and trimannosylchitobiose core glycans. In particular, the Manα1,6Manβ1,4GlcNAc(α1,6Fuc)β1,4GlcNAcβAsn glycan (M2F) decorates various human neutrophil proteins reportedly displaying bioactivity and structural integrity demonstrating that they are not degradation products. Less-truncated paucimannosidic glycans (e.g. M3F) are characteristic glycosylation features of proteins expressed by human cancer and stem cells. Concertedly, these observations suggest the involvement of human PMPs in processes related to innate immunity, tumorigenesis and cellular differentiation. The absence of human PMPs in diverse bodily fluids studied under many (patho)physiological conditions suggests extravascular residence and points to localised functions of PMPs in peripheral tissues. Absence of PMPs in Fungi indicates that paucimannosylation is common, but not universally conserved, in eukaryotes. Relative to human PMPs, the expression of PMPs in plants, invertebrates and protists is more tissue-wide and constitutive yet, similar to their human counterparts, PMP expression remains regulated by the physiology of the producing organism and PMPs evidently serve essential functions in development, cell-cell communication and host-pathogen/symbiont interactions. In most PMP-producing organisms, including humans, the N-acetyl-β-hexosaminidase isoenzymes and linkage-specific α-mannosidases are glycoside hydrolases critical for generating PMPs via N-acetylglucosaminyltransferase I (GnT-I)-dependent and GnT-I-independent truncation pathways. However, the identity and structure of many species-specific PMPs in eukaryotes, their biosynthetic routes, strong tissue- and development-specific expression, and diverse functions are still elusive. Deep exploration of these PMP features involving, for example, the characterisation of endogenous PMP-recognising lectins across a variety of healthy and N-acetyl-β-hexosaminidase-deficient human tissue types and identification of microbial adhesins reactive to human PMPs, are amongst the many tasks required for enhanced insight into the glycobiology of human PMPs. In conclusion, the literature supports the notion that PMPs are significant, yet still heavily under-studied biomolecules in human glycobiology that serve essential functions and create structural heterogeneity not dissimilar to other human N-glycoprotein types. Human PMPs should therefore be recognised as bioactive glycoproteins that are distinctly different from the canonical N-glycoprotein classes and which warrant a more dedicated focus in glycobiological research.

innate immunity, N-glycosylation, glycobiology, eukaryote, N-acetyl-β-hexosaminidase, N -acetylglucosaminyltransferase I, paucimannosidic protein, paucimannosylation

Structure type: fragment of a bigger structure
Location inside paper: p. 2083
Aglycon: lipid
Compound class: glycoinositol phospholipid
Contained glycoepitopes: IEDB_130701,IEDB_141793,IEDB_141807,IEDB_144983,IEDB_151531,IEDB_152206,IEDB_153220,IEDB_983930,SB_198,SB_44,SB_67,SB_72

Comments, role: review

NCBI Taxonomy refs (TaxIDs): 5693, 5691, 5658
Show glycosyltransferases

There is only one chemically distinct structure:

N[C@H]1[C@H](O[C@@H]2[C@@H](OP(=O)(O)O)[C@@H](O)[C@@H](O)[C@H](O)[C@H]2O)O[C@H](CO)[C@@H](O[C@H]2O[C@H](CO[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]3O)[C@@H](O)[C@H](O)[C@@H]2O)[C@@H]1O

SVG MW SMILES 3D mol Ionize