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

, ICD11: XN56V

]; infection due to Trypanosoma cruzi [ICD11: XN56V

]

NCBI PubMed ID: 24489949
Publication DOI: 10.1371/journal.pone.0087673
Journal NLM ID: 101285081
Publisher: San Francisco, CA: Public Library of Science
Correspondence: taron

neb.com
Institutions: New England Biolabs, Ipswich, Massachusetts, United States of America, New England Biolabs, Ipswich, USA

The glycosylphosphatidylinositol (GPI) anchor is an essential glycolipid that tethers certain eukaryotic proteins to the cell surface. The core structure of the GPI anchor is remarkably well conserved across evolution and consists of NH2-CH2-CH2-PO4-6Manα1,2Manα1,6Manα1,4-GlcNα1,6-myo-inositol-PO4-lipid. The glycan portion of this structure may be modified with various side-branching sugars or other compounds that are heterogeneous and differ from organism to organism. One such modification is an α(1,2)-linked fourth mannose (Man-IV) that is side-branched to the third mannose (Man-III) of the trimannosyl core. In fungi and mammals, addition of Man-III and Man-IV occurs by two distinct Family 22 α(1,2)-mannosyltransferases, Gpi10/PigB and Smp3/PigZ, respectively. However, in the five protozoan parasite genomes we examined, no genes encoding Smp3/PigZ proteins were observed, despite reports of tetramannosyl-GPI structures (Man4-GPIs) being produced by some parasites. In this study, we tested the hypothesis that the Gpi10/PigB proteins produced by protozoan parasites have the ability to add both Man-III and Man-IV to GPI precursors. We used yeast genetics to test the in vivo specificity of Gpi10/PigB proteins from several Plasmodium and Trypanosoma species by examining their ability to restore viability to Saccharomyces cerevisiae strains harboring lethal defects in Man-III (gpi10Δ) or Man-IV (smp3Δ) addition to GPI precursor lipids. We demonstrate that genes encoding PigB enzymes from T. cruzi, T. congolense and P. falciparum are each capable of separately complementing essential gpi10Δ and smp3Δ mutations, while PIGB genes from T. vivax and T. brucei only complement gpi10Δ. Additionally, we show the ability of T. cruzi PIGB to robustly complement a gpi10Δ/smp3Δ double mutant. Our data suggest that certain Plasmodium and Trypanosoma PigB mannosyltransferases can transfer more than one mannose to GPI precursors in vivo, and suggest a novel biosynthetic mechanism by which Man4-GPIs may be synthesized in these organisms.

glycan, Glycosylphosphatidylinositol, Mannosyltransferase, Plasmodium, GPI, protozoan, Trypanosoma, Saccharomyces cerevisiae

Structure type: oligomer
Location inside paper: Fig. 1, Table 1
Compound class: GPI-anchor
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_130701,IEDB_136104,IEDB_140116,IEDB_141793,IEDB_141807,IEDB_141829,IEDB_141830,IEDB_141832,IEDB_143632,IEDB_144983,IEDB_151531,IEDB_152206,IEDB_153220,IEDB_474450,IEDB_76933,IEDB_983930,SB_136,SB_191,SB_196,SB_198,SB_44,SB_67,SB_72

Methods: PCR, genetic methods, BLASTp

Related record ID(s): 4847, 7278
NCBI Taxonomy refs (TaxIDs): 5693
Show glycosyltransferases

There is only one chemically distinct structure:

[1*]OCC(COP(=O)(O)O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O[C@H]1O[C@H](COP(=O)(O)CCN)[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]3O[C@H](COP(=O)(O)OCCN[3*])[C@@H](O)[C@H](O)[C@@H]3O[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](O)[C@H]1N)O[2*]

SVG MW SMILES 3D mol Ionize

R1 = ALK
R2 = LIP
R3 = protein