ArticlePLoS biology2012
A Toxoplasma gondii pseudokinase inhibits host IRG resistance proteins.
Article in PLoS biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 183 citations in OpenAlex.
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- Trx4, a novel thioredoxin protein, is important for Toxoplasma gondii fitness.Parasites & vectors · 2024Article
- Toxoplasma protein export and effector function.Nature microbiology · 2024Review
- IFNs in host defence and parasite immune evasion duringFrontiers in immunology · 2024Review
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- A heterotrimeric complex of Toxoplasma proteins promotes parasite survival in interferon gamma-stimulated human cells.PLoS biology · 2023Article
- Multiple pals gene modules control a balance between immunity and development in Caenorhabditis elegans.PLoS pathogens · 2023Article
- MultiplebioRxiv : the preprint server for biology · 2023Article
- ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence.PLoS pathogens · 2023Article
- Variation in CD8 T cell IFNγ differentiation to strains ofFrontiers in cellular and infection microbiology · 2023Article
- Toxoplasma gondii virulence factor ROP1 reduces parasite susceptibility to murine and human innate immune restriction.PLoS pathogens · 2022Article
- Screening the Toxoplasma kinome with high-throughput tagging identifies a regulator of invasion and egress.Nature microbiology · 2022Article
- IFN-induced cell-autonomous immune mechanisms in the control of intracellular protozoa.Parasitology research · 2022Review
- Released Parasite-Derived Kinases as Novel Targets for Antiparasitic Therapies.Frontiers in cellular and infection microbiology · 2022Review
- Article
- The pathogenicity and virulence ofVirulence · 2021Article
- Secreted Effectors Modulating Immune Responses toLife (Basel, Switzerland) · 2021Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The ability of mice to resist infection with the protozoan parasite, Toxoplasma gondii, depends in large part on the function of members of a complex family of atypical large GTPases, the interferon-gamma-inducible immunity-related GTPases (IRG proteins). Nevertheless, some strains of T. gondii are highly virulent for mice because, as recently shown, they secrete a polymorphic protein kinase, ROP18, from the rhoptries into the host cell cytosol at the moment of cell invasion. Depending on the allele, ROP18 can act as a virulence factor for T. gondii by phosphorylating and thereby inactivating mouse IRG proteins. In this article we show that IRG proteins interact not only with ROP18, but also strongly with the products of another polymorphic locus, ROP5, already implicated as a major virulence factor from genetic crosses, but whose function has previously been a complete mystery. ROP5 proteins are members of the same protein family as ROP18 kinases but are pseudokinases by sequence, structure, and function. We show by a combination of genetic and biochemical approaches that ROP5 proteins act as essential co-factors for ROP18 and present evidence that they work by enforcing an inactive GDP-dependent conformation on the IRG target protein. By doing so they prevent GTP-dependent activation and simultaneously expose the target threonines on the switch I loop for phosphorylation by ROP18, resulting in permanent inactivation of the protein. This represents a novel mechanism in which a pseudokinase facilitates the phosphorylation of a target by a partner kinase by preparing the substrate for phosphorylation, rather than by upregulation of the activity of the kinase itself.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.