ArticleMolecular microbiology2017
Membrane skeletal association and post-translational allosteric regulation of Toxoplasma gondii GAPDH1.
Article in Molecular microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- The aldehyde dehydrogenase superfamilies: correlations and deviations in structure and function.Applied microbiology and biotechnology · 2025Review
- TgLaforin, a glucan phosphatase, reveals the dynamic role of storage polysaccharides inbioRxiv : the preprint server for biology · 2024Article
- Protein kinases on carbon metabolism: potential targets for alternative chemotherapies against toxoplasmosis.Frontiers in cellular and infection microbiology · 2023Review
- Two apicoplast dwelling glycolytic enzymes provide key substrates for metabolic pathways in the apicoplast and are critical for Toxoplasma growth.PLoS pathogens · 2022Article
- Global profiling of protein lysine malonylation in Toxoplasma gondii strains of different virulence and genetic backgrounds.PLoS neglected tropical diseases · 2022Article
- Fussing About Fission: Defining Variety Among Mainstream and Exotic Apicomplexan Cell Division Modes.Frontiers in cellular and infection microbiology · 2020Article
- Global Proteomic Analysis of Lysine Malonylation inFrontiers in microbiology · 2020Article
- Identification of Alternative Allosteric Sites in Glycolytic Enzymes for Potential Use as Species-Specific Drug Targets.Frontiers in molecular biosciences · 2020Article
- Toxoplasma F-box protein 1 is required for daughter cell scaffold function during parasite replication.PLoS pathogens · 2019Article
- CSGID Solves Structures and Identifies Phenotypes for Five Enzymes inFrontiers in cellular and infection microbiology · 2018Article
- Article
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Authors and funding
7 authors.
Funding
Abstract
When Toxoplasma gondii egresses from the host cell, glyceraldehyde-3-phosphate dehydrogenase 1 (GAPDH1), which is primary a glycolysis enzyme but actually a quintessential multifunctional protein, translocates to the unique cortical membrane skeleton. Here, we report the 2.25 Å resolution crystal structure of the GAPDH1 holoenzyme in a quaternary complex providing the basis for the molecular dissection of GAPDH1 structure-function relationships Knockdown of GAPDH1 expression and catalytic site disruption validate the essentiality of GAPDH1 in intracellular replication but we confirmed that glycolysis is not strictly essential. We identify, for the first time, S-loop phosphorylation as a novel, critical regulator of enzymatic activity that is consistent with the notion that the S-loop is critical for cofactor binding, allosteric activation and oligomerization. We show that neither enzymatic activity nor phosphorylation state correlate with the ability to translocate to the cortex. However, we demonstrate that association of GAPDH1 with the cortex is mediated by the N-terminus, likely palmitoylation. Overall, glycolysis and cortical translocation are functionally decoupled by post-translational modifications.
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Registered trials
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