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Functional characterization of the orphan hypothetical protein TGGT1_245740, a transmembrane protein required for Toxoplasma gondii growth and virulence II

ABSTRACT: Numerous hypothetical proteins in Toxoplasma gondii (T. gondii) are predicted to participate in diverse biological processes. TGGT1_245740, characterized in this study, is annotated as a hypothetical protein lacking identifiable orthologs, conserved domains, and intrinsically disordered regions (IDRs), suggesting that it represents an orphan protein in T. gondii, a class that remains largely unexplored. In this study, the biological function of TGGT1_245740 was investigated through bioinformatic analysis, monoclonal antibody production, expression profiling, gene tagging, gene knockout, phenotypic assays, and transcriptomic analysis. TGGT1_245740 was found to be diffusely distributed in the inner membrane complex (IMC). The knockout of TGGT1_245740 gene could reduce the intracellular proliferation and virulence of the parasite. The host transcriptome suggested that infection with the knockout strain enhanced the host immune response, and the two sets of data together further revealed the potential role of the protein in regulating parasite metabolic homeostasis and host immune recognition. This study provides the first functional characterization of this orphan protein, highlighting its potential role in the physiological metabolism and host–parasite interaction of T. gondii.

ORGANISM(S): Homo sapiens

PROVIDER: GSE335016 | GEO | 2026/06/17

REPOSITORIES: GEO

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Functional characterization of the orphan hypothetical protein TGGT1_245740, a transmembrane protein required for Toxoplasma gondii growth and virulence.

Project description:Numerous hypothetical proteins in Toxoplasma gondii (T. gondii) are predicted to participate in diverse biological processes. TGGT1_245740, characterized in this study, is annotated as a hypothetical protein lacking identifiable orthologs, conserved domains, and intrinsically disordered regions (IDRs), suggesting that it represents an orphan protein in T. gondii, a class that remains largely unexplored. In this study, the biological function of TGGT1_245740 was investigated through bioinformatic analysis, monoclonal antibody production, expression profiling, gene tagging, gene knockout, phenotypic assays, and transcriptomic analysis. TGGT1_245740 was found to be diffusely distributed in the inner membrane complex (IMC). The knockout of TGGT1_245740 gene could reduce the intracellular proliferation and virulence of the parasite. The host transcriptome suggested that infection with the knockout strain enhanced the host immune response, and the two sets of data together further revealed the potential role of the protein in regulating parasite metabolic homeostasis and host immune recognition. This study provides the first functional characterization of this orphan protein, highlighting its potential role in the physiological metabolism and host–parasite interaction of T. gondii.

2026-06-17 | GSE334992 | GEO

A Gain-of-Function Genomic Screen Identifies the Orphan Nuclear Receptor TLX as an Enhancer of STAT1-mediated Transcription and Immunity to Toxoplasma gondii: TLX overexpression

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2015-05-29 | GSE55749 | GEO

A Gain-of-Function Genomic Screen Identifies the Orphan Nuclear Receptor TLX as an Enhancer of STAT1-mediated Transcription and Immunity to Toxoplasma gondii: TLX siRNA

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Project description:Plasmodium immune evasion strategies hugely contribute to the success of parasite in its host and of various immune evasion strategies, parasite often expresses molecular mimics of host molecules to manipulate the host responses. In this study, we report a Plasmodium hypothetical protein which is homologous to its human T cell immunomodulatory protein and possess the potential to suppress the immune responses. This Plasmodium berghei protein, PbTIP, is expressed as a surface protein of merozoites and reduce inflammatory response of macrophages while up-regulating the anti-inflammatory cytokines such as TGF-β and IL-10 in-vitro. The immunosuppressive effect of PbTIP was studies systemically by treating mouse with recombinant PbTIP (10mg/kg) for four consecutive days followed by mouse PBMCs isolation and transcriptome profiling. GST protein treated mouse PBMCs were taken as control here.

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2022-07-25 | PXD032362 | Pride

Host cell subversion by Toxoplasma GRA16, a HAUSP- and PP2A-interacting protein exported to the host cell nucleus

Project description:Toxoplasma gondii multiplies inside a parasitophorous vacuole in the host cell. Several parasite proteins have been described that hijack host signaling pathways, which mostly originate from the rhoptry organelles. We report here the identification and characterization of GRA16, the first dense granule protein shown to be exported through the parasitophorous vacuole membrane and to reach the host cell nucleus. Transcriptomic analysis revealed that GRA16 positively modulates the expression of host genes involved in cell-cycle progression and the p53 tumor suppressor pathway. We show that GRA16 directly binds two host enzymes, the deubiquitinase HAUSP and the phosphatase PP2A, and that GRA16 alters p53 protein levels in a HAUSP-dependent manner and induces the nuclear translocation of the PP2A holoenzyme. Therefore GRA16 is a novel regulator of the HAUSP/p53 pathway and together with GRA15, emerge as a subfamily of new dense granule proteins exported beyond the tachyzoites-hosting vacuole to subvert the host transcriptome. Mouse bone marrow-derived macrophages (BMDM) or Human foreskin fibroblasts (HFFs) were infected with the following Toxoplasma gondii strains: - RHku80 WT versus RHku80(deltaGRA16) mutant (in BMDM) - Pruku80 WT versus Pruku80(deltaGRA16) mutant (in BMDM) - RHku80 WT versus RHku80(deltaGRA16) mutant (in HFF)

2013-02-06 | E-GEOD-38779 | biostudies-arrayexpress

A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation

Project description:Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan parasite that resides inside a parasitophorous vacuole. During infection, Toxoplasma actively remodels the transcriptome of its hosting cells with profound and coupled impact on the host immune response. We report that Toxoplasma secretes GRA24, a novel dense granule protein which traffics from the vacuole to the host cell nucleus. Once released into the host cell, GRA24 has the unique ability to trigger prolonged autophosphorylation and nuclear translocation of the host cell p38M-NM-1 MAP kinase. This noncanonical kinetics of p38M-NM-1 activation correlates with the up-regulation of the transcription factors Egr-1 and c-Fos and the correlated synthesis of key proinflammatory cytokines, including interleukin-12 and the chemokine MCP-1, both known to control early parasite replication in vivo. Remarkably, the GRA24-p38M-NM-1 complex is defined by peculiar structural features and uncovers a new regulatory signaling path distinct from the MAPK signaling cascade and otherwise commonly activated by stress-related stimuli or various intracellular microbes. GRA24 = PSP7 Mouse bone marrow-derived macrophages (BMDM) were infected with the following Toxoplasma gondii strains: - RHku80 WT versus RHku80(deltaPSP7) mutant - Pruku80 WT versus Pruku80(deltaPSP7) mutant

2013-09-01 | E-GEOD-38782 | biostudies-arrayexpress

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2024-05-05 | GSE266204 | GEO

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