Affinage · Toxoplasma gondii

DPA

deoxyribose-phosphate aldolase · UniProt A0A125YRB4

Annotated
2026-09-08
3 papers in source corpus 3 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TgDPA is a bradyzoite-specific protein of Toxoplasma gondii that has repurposed an aldolase scaffold into an actin-regulatory function (PMID:18950626, PMID:25284756). Although it carries a deoxyribose phosphate aldolase (DeoC) domain and adopts a TIM barrel fold, it lacks the key catalytic residues of the canonical DERA family and is enzymatically inactive on the dR5P substrate (PMID:25284756). Instead, TgDPA binds polymerized actin directly and physically interacts with the actin depolymerizing factor TgADF, enhancing TgADF activity to lower actin polymerization and promote filament disassembly in vitro (PMID:20433874, PMID:25284756). Through this activity it modulates actin filament dynamics in the bradyzoite stage, where it is expressed specifically both in vivo and in vitro (PMID:18950626). Beyond this actin-regulatory role, no additional mechanistic function has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2008 Medium

    Establishing when and where TgDPA is expressed was necessary to place the aldolase-domain protein in a biological context; stage-specific expression defined it as a bradyzoite marker.

    Evidence RT-PCR, qPCR, and immunofluorescence with an anti-recombinant TgDPA antibody in T. gondii

    PMID:18950626

    Open questions at the time
    • No functional mechanism established
    • Catalytic competence of the DeoC domain untested
    • Single lab
  2. 2010 Medium

    Whether TgDPA had a role beyond a putative metabolic enzyme was unknown; identifying TgADF as a binding partner and measuring functional consequences revealed an actin-regulatory role.

    Evidence Yeast two-hybrid, Co-IP, GST pull-down, and in vitro actin polymerization/disassembly kinetics assays in T. gondii

    PMID:20433874

    Open questions at the time
    • In vivo consequence of the TgDPA-TgADF interaction not tested
    • Whether actin regulation depends on aldolase activity unresolved at this point
    • Single lab
  3. 2014 High

    It was unclear whether TgDPA retained aldolase activity or acted purely as an actin-binding scaffold; structural and biochemical analysis showed it is catalytically dead yet binds actin, reconciling the aldolase fold with the actin-regulatory function.

    Evidence X-ray crystallography, structural comparison to DERA, dR5P biochemical activity assays, and in vitro actin binding in T. gondii

    PMID:25284756

    Open questions at the time
    • Structural basis of the actin/TgADF interaction not resolved
    • In vivo requirement of TgDPA for bradyzoite actin dynamics untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological role of TgDPA-mediated actin regulation in bradyzoite biology, and whether it is required for cyst formation or persistence, remains unresolved.
  • No genetic knockout/knockdown phenotype in the corpus
  • No in vivo functional consequence established
  • Structural model of the actin-binding interface lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
POLYMERIZED ACTINTGADF (ACTIN DEPOLYMERIZING FACTOR)

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 TgDPA encodes a 286 amino acid protein (~31 kDa) with a deoxyribose phosphate aldolase (DeoC) domain (~30% homology to E. coli DeoC); immunofluorescent analysis with a polyclonal antibody against recombinant TgDPA demonstrated that the protein is expressed specifically in bradyzoites both in vivo and in vitro, establishing it as a bradyzoite-specific marker. RT-PCR, quantitative PCR, recombinant protein expression, immunofluorescence assay Experimental parasitology Medium 18950626
2010 TgDPA physically interacts with actin depolymerizing factor (TgADF), as shown by yeast two-hybrid screening, co-immunoprecipitation, and GST pull-down assay; addition of GST-TgDPA to TgADF lowered the extent of actin polymerization and enhanced filamentous actin disassembly in vitro, indicating TgDPA enhances TgADF activity to promote actin filament dynamics in bradyzoites. Yeast two-hybrid, co-immunoprecipitation, GST pull-down, actin polymerization and disassembly kinetics assay Molecular and biochemical parasitology Medium 20433874
2014 Crystal structure of TgDPA revealed a TIM barrel fold with key catalytic residues absent compared to canonical deoxyribose-5-phosphate aldolase (DERA) family members; consistent with this, biochemical assays showed TgDPA is catalytically inactive on dR5P substrate. Despite lacking enzymatic activity, TgDPA is competent to bind polymerized actin in vitro, similar to TgALD1. X-ray crystallography, structural comparison, biochemical activity assays (dR5P substrate), in vitro actin binding assay Journal of molecular biology High 25284756

Source papers

Stage 0 corpus · 3 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Toxoplasma gondii: Identification and characterization of bradyzoite-specific deoxyribose phosphate aldolase-like gene (TgDPA). Experimental parasitology 22 18950626
2014 Structural and functional divergence of the aldolase fold in Toxoplasma gondii. Journal of molecular biology 11 25284756
2010 Toxoplasma gondii deoxyribose phosphate aldolase-like protein (TgDPA) interacts with actin depolymerizing factor (TgADF) to enhance the actin filament dynamics in the bradyzoite stage. Molecular and biochemical parasitology 6 20433874