Affinage · Toxoplasma gondii

TGME49_251550

acyl-CoA binding protein ACBP1 · UniProt A0A125YSH4

Annotated
2026-09-08
1 papers in source corpus 1 papers cited in narrative 4 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TgACBP1 is a cytosolic acyl-CoA binding protein of Toxoplasma gondii that binds long-chain acyl-CoA esters and functions in fatty acid elongation and glycerophospholipid biosynthesis (PMID:30362657). Its acyl-CoA binding activity is established by direct fluorimetric binding and by rescue in a yeast complementation assay (PMID:30362657). Loss of TgACBP1 alone reduces C18:1 fatty acid abundance without an overt growth phenotype, but combined disruption of TgACBP1 and TgSCP2 synergistically impairs intracellular growth and murine virulence (PMID:30362657), further depletes long- and very-long-chain fatty acids (C18:1, C22:1, C24:1) and their synthesis rates (PMID:30362657), and causes severe defects in glyceride and phospholipid production (PMID:30362657), placing the two proteins in a shared, partially redundant lipid-transport pathway. Beyond this single study, no further mechanistic detail has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2018 Medium

    Whether TgACBP1 actually binds acyl-CoA and behaves as a functional acyl-CoA transporter was unknown; biochemical binding and cross-species rescue established it as a bona fide cytosolic acyl-CoA binding protein.

    Evidence Fluorimetric acyl-CoA binding assay and yeast complementation in Toxoplasma gondii

    PMID:30362657

    Open questions at the time
    • No structural basis for acyl-CoA selectivity
    • Range of acyl-chain lengths bound not fully delineated
  2. 2018 Medium

    It was unclear whether TgACBP1 is individually essential; genetic disruption showed it is dispensable alone but functionally redundant with TgSCP2, revealing synergistic control of growth and virulence.

    Evidence Single and double genetic knockouts with intracellular growth and mouse virulence assays in Toxoplasma gondii

    PMID:30362657

    Open questions at the time
    • Molecular basis of TgACBP1/TgSCP2 redundancy not defined
    • Whether the two proteins physically interact or act sequentially unresolved
  3. 2018 Medium

    The metabolic consequence of losing TgACBP1 was unknown; lipidomic and isotope-tracing analyses linked it to fatty acid elongation, showing reduced C18:1 alone and broader long-/very-long-chain fatty acid defects when combined with TgSCP2 loss.

    Evidence GC-MS lipidomics with 13C-labelling in Toxoplasma gondii

    PMID:30362657

    Open questions at the time
    • Direct coupling of acyl-CoA transport to specific elongase reactions not shown
    • Contribution to individual elongation steps not resolved
  4. 2018 Medium

    Whether the fatty acid defects propagate to membrane lipid synthesis was open; lipidomics showed double disruption severely impairs glyceride and phospholipid production, placing TgACBP1 upstream of glycerophospholipid biosynthesis.

    Evidence HPLC-HRMS lipidomic analysis of knockout parasites in Toxoplasma gondii

    PMID:30362657

    Open questions at the time
    • Specific phospholipid species affected not fully catalogued
    • Whether defect is direct substrate-supply or indirect not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TgACBP1 physically and functionally coordinates with TgSCP2, its structural determinants of acyl-CoA binding, and its regulation within the parasite lipid network remain uncharacterized.
  • No reported protein-protein interaction data for TgACBP1/TgSCP2
  • No structural model of TgACBP1
  • No evidence spanning multiple T. gondii strains

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
TGSCP2

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 TgACBP1 possesses acyl-CoA binding activity, confirmed by fluorimetric binding assay and yeast complementation, functioning as a cytosolic acyl-CoA transporter for long-chain acyl-CoA esters in Toxoplasma lipid metabolism. Fluorimetric binding assay and yeast complementation assay Cellular Microbiology Medium 30362657
2018 Disruption of TgACBP1 alone causes no obvious growth phenotype, but double disruption of TgACBP1 and TgSCP2 results in defects in intracellular growth and reduced virulence in mice, demonstrating synergistic roles in lipid metabolism. Genetic disruption (single and double knockout), intracellular growth assay, mouse virulence assay Cellular Microbiology Medium 30362657
2018 Disruption of TgACBP1 alone leads to decreased abundance of C18:1 fatty acid; double disruption of TgACBP1 and TgSCP2 further reduces C18:1, C22:1, and C24:1 abundance and decreases synthesis rates of C18:0, C22:1, and C24:1, indicating TgACBP1 contributes to fatty acid elongation/transport. Gas chromatography-mass spectrometry (GC-MS) and 13C-labelling assay combined with GC-MS Cellular Microbiology Medium 30362657
2018 Double disruption of TgACBP1 and TgSCP2 causes serious defects in production of glycerides and phospholipids, placing TgACBP1 in a pathway required for glycerophospholipid biosynthesis. HPLC coupled with high-resolution mass spectrometry (HPLC-HRMS) lipidomic analysis Cellular Microbiology Medium 30362657

Source papers

Stage 0 corpus · 1 paper · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Synergistic roles of acyl-CoA binding protein (ACBP1) and sterol carrier protein 2 (SCP2) in Toxoplasma lipid metabolism. Cellular microbiology 13 30362657