Affinage · Toxoplasma gondii

GP

putative glycogen phosphorylase 1 · UniProt S8EYF4

Annotated
2026-09-10
10 papers in source corpus 1 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TgGP (putative glycogen phosphorylase) is the enzyme responsible for amylopectin catabolism in Toxoplasma gondii bradyzoites, and its activity is governed by phosphorylation of Ser25: a phosphorylation-null mutant (S25A) and a truncation mutant (S25stop) accumulate amylopectin, whereas a phosphomimetic mutant (S25E) shows minimal accumulation, establishing that Ser25 phosphorylation activates TgGP to drive amylopectin digestion (PMID:28851850). Tight control of this activity is required for chronic infection, as both loss of activity (S25A) and constitutive activity (S25E) reduce brain cyst production in mice, while complementation restoring normal amylopectin regulation restores cyst formation (PMID:28851850). Beyond this phosphoregulated role in amylopectin turnover, no further mechanistic detail about TgGP has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2017 High

    It was unknown which enzyme degrades the bradyzoite storage polysaccharide amylopectin and how it is controlled; separation-of-function mutants established that TgGP drives amylopectin catabolism and is switched on by Ser25 phosphorylation.

    Evidence Site-directed mutagenesis (S25stop, S25A, S25E) with CRISPR editing, amylopectin staining, and complementation rescue in T. gondii Pru

    PMID:28851850

    Open questions at the time
    • The kinase and phosphatase acting on Ser25 are not identified in this finding
    • No direct biochemical demonstration of phosphorylase catalytic activity on amylopectin substrate
  2. 2017 High

    It was unknown whether the balance of amylopectin turnover matters for chronic infection; gain- and loss-of-function TgGP mutants showed that both constitutive inactivation and constitutive activation impair brain cyst formation, establishing that tight regulation of TgGP is required in vivo.

    Evidence Mouse infection model with cyst quantification and complementation rescue in T. gondii Pru

    PMID:28851850

    Open questions at the time
    • Does not resolve how amylopectin flux mechanistically supports cyst maturation
    • Upstream regulatory signals controlling TgGP activity in vivo are not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 TgGP (glycogen phosphorylase) is required for amylopectin catabolism in Toxoplasma gondii bradyzoites; a stop codon mutant (S25stop) and a phosphorylation-null mutant (S25A) both display amylopectin accumulation, while a phosphorylation-mimetic mutant (S25E) shows minimal amylopectin accumulation under both tachyzoite and bradyzoite growth conditions, establishing that phosphorylation of Ser25 activates TgGP to drive amylopectin digestion. Site-directed mutagenesis (S25stop, S25A, S25E) combined with CRISPR/genome editing, amylopectin staining, and complementation rescue experiments in T. gondii mBio High 28851850
2017 Both loss of TgGP activity (S25A inactive mutant) and constitutive TgGP activity (S25E hyperactive mutant) significantly reduced brain cyst production in mice compared to wild-type, and complementation restoring normal amylopectin regulation restored cyst production to control levels, establishing that tight TgGP-mediated regulation of amylopectin is required for efficient cyst formation. Mouse infection model with cyst quantification, complementation experiment mBio High 28851850

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis. Pathogens (Basel, Switzerland) 82 32245165
2017 Toxoplasma gondii Requires Glycogen Phosphorylase for Balancing Amylopectin Storage and for Efficient Production of Brain Cysts. mBio 50 28851850
2022 In vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization. Nature communications 46 35246532
2020 Toxoplasma gondii α-amylase deletion mutant is a promising vaccine against acute and chronic toxoplasmosis. Microbial biotechnology 27 32959958
2023 Rapid metabolic reprogramming mediated by the AMP-activated protein kinase during the lytic cycle of Toxoplasma gondii. Nature communications 21 36702847
2022 The determinants regulating Toxoplasma gondii bradyzoite development. Frontiers in microbiology 16 36439853
2024 Metabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii. Nature communications 11 38589375
2021 Lysine crotonylation is widespread on proteins of diverse functions and localizations in Toxoplasma gondii. Parasitology research 5 33655350
2025 Dynamics of amylopectin granule accumulation during the course of chronic Toxoplasma infection is linked to intra-cyst bradyzoite replication. mSphere 4 40492719
2024 PP1 phosphatase controls both daughter cell formation and amylopectin levels in Toxoplasma gondii. PLoS biology 4 39255306