Affinage · Toxoplasma gondii

DPY19

Q-cell neuroblast polarisation protein · UniProt A0A125YSP7

Annotated
2026-09-08
2 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Toxoplasma gondii DPY19 is a protein C-mannosyltransferase that installs α-mannose on tryptophan residues within the WXXWXXC motif of thrombospondin type 1 repeat (TSR) domains, modifying the micronemal adhesin MIC2 (PMID:29432542). Genetic deletion of dpy19 abolishes parasite C-mannosyltransferase activity and reduces MIC2 protein levels, establishing DPY19 as the enzyme responsible for TSR C-mannosylation in the parasite (PMID:31862733). This modification supports parasite adhesion to host cells, gliding motility, host cell invasion and egress, and full virulence in mice; the virulence defect exceeds what reduced MIC2 alone can explain, indicating additional DPY19 substrates beyond MIC2 (PMID:31862733). Unlike C. elegans or mammalian C-mannosyltransferases, the T. gondii enzyme is inactive on a short WXXW peptide in vitro, a substrate-specificity distinction whose structural basis has not been characterized in the available corpus (PMID:29432542).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2018 High

    It was unknown whether the T. gondii Dpy19 homolog possessed C-mannosyltransferase activity; reconstituting the enzyme and detecting the modification established that it transfers mannose to tryptophan within the WXXWXXC motif of MIC2 TSR domains.

    Evidence In vitro C-mannosyltransferase peptide assay, complementation in a mammalian C-mannosylation-deficient cell line, and mass spectrometry of MIC2

    PMID:29432542

    Open questions at the time
    • Structural basis for inactivity on short WXXW peptides versus full TSR domains not resolved
    • Full substrate repertoire beyond MIC2 not defined
    • Catalytic mechanism and cofactor requirements not detailed
  2. 2019 High

    It was unclear whether DPY19 is the physiological enzyme for TSR C-mannosylation and what its loss costs the parasite; knockout abolished activity, lowered MIC2, and impaired the full invasion program, establishing DPY19 as required for adhesion, motility, invasion, egress and virulence.

    Evidence Δdpy19 knockout with C-mannosyltransferase activity assay, MIC2 Western blot, adhesion/motility/invasion/egress assays, and mouse virulence model

    PMID:31862733

    Open questions at the time
    • Additional C-mannosylated substrates responsible for the excess virulence defect not identified
    • Mechanistic link between C-mannosylation and MIC2 stability not delineated
    • How reduced modification translates to weakened adhesion at the molecular level not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of DPY19 substrates beyond MIC2 that account for its full contribution to virulence remains unresolved.
  • No additional C-mannosylated adhesins have been mapped in the corpus
  • No structural model explaining TSR-specific versus peptide substrate recognition

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
MIC2 (MICRONEMAL TSR-CONTAINING ADHESIN, SUBSTRATE)

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 Toxoplasma gondii DPY19 (Dpy19 homolog) functions as a C-mannosyltransferase that modifies thrombospondin type 1 repeat (TSR) domains of the micronemal adhesin MIC2, transferring mannose to tryptophan residues within the WXXWXXC motif. When expressed in a mammalian cell line deficient in C-mannosylation, the T. gondii Dpy19 homolog was able to C-mannosylate TSR-containing adhesins; however, unlike C. elegans or mammalian C-mannosyltransferases, it was inactive on a short WXXW peptide in vitro. In vitro C-mannosyltransferase assay with peptide substrates; complementation in mammalian C-mannosylation-deficient cell line; mass spectrometry detection of C-hexosylation on MIC2 Glycobiology High 29432542
2019 Deletion of the dpy19 gene in T. gondii abolished C-mannosyltransferase activity and reduced levels of the micronemal protein MIC2, establishing DPY19 as the enzyme responsible for C-mannosylation of TSR-containing proteins in the parasite. Loss of DPY19 activity caused weakened parasite adhesion to host cells, reduced motility, impaired host cell invasion and egress, and strong attenuation of virulence in mice, with the virulence defect exceeding what can be explained by reduced MIC2 alone, indicating that additional substrates are C-mannosylated by DPY19. Genetic knockout (Δdpy19) with C-mannosyltransferase activity assay, Western blot for MIC2 levels, adhesion assay, motility assay, invasion and egress assays, mouse virulence model The Journal of biological chemistry High 31862733

Source papers

Stage 0 corpus · 2 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Apicomplexan C-Mannosyltransferases Modify Thrombospondin Type I-containing Adhesins of the TRAP Family. Glycobiology 21 29432542
2019 C-Mannosylation of Toxoplasma gondii proteins promotes attachment to host cells and parasite virulence. The Journal of biological chemistry 11 31862733