Evidence map›Paper›PMID 25118287›Full record

ArticleThe Journal of biological chemistry2014

The Toxoplasma pseudokinase ROP5 is an allosteric inhibitor of the immunity-related GTPases.

Michael L Reese, Niket Shah, John C Boothroyd

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed.

  1. Article
  2. Article
  3. Cysteine-S-nitrosylation inhibits Rop5-mediated immune evasion inbioRxiv : the preprint server for biology · 2025
    Article
  4. Article
  5. Article
  6. NcROP2 deletion reducesFrontiers in immunology · 2025
    Article
  7. Article
  8. International journal of molecular sciences · 2024
    Article
  9. Review
  10. Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I.Genes to cells : devoted to molecular & cellular mechanisms · 2024
    Article
  11. Variation in CD8 T cell IFNγ differentiation to strains ofFrontiers in cellular and infection microbiology · 2023
    Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. The Host Autophagy DuringFrontiers in microbiology · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Michael L ReeseFrom the Departments of Microbiology and Immunology, and.
Niket Shahthe Molecular and Cellular Physiology, and Structural Biology, Stanford University, Stanford, California 94305.
John C BoothroydFrom the Departments of Microbiology and Immunology, and john.boothroyd@stanford.edu.

Funding

Strain-specific Host-Pathogen Interactions in ToxoplasmosisR01AI073756 · NIAID · STANFORD UNIVERSITY · PI BOOTHROYD, JOHN C · 2007 to 2016
$4.2M
NIAID NIH HHS AI73756NIAID NIH HHS R01 AI073756
6 · The paper itself

Abstract

The Red Queen hypothesis proposes that there is an evolutionary arms race between host and pathogen. One possible example of such a phenomenon could be the recently discovered interaction between host defense proteins known as immunity-related GTPases (IRGs) and a family of rhoptry pseudokinases (ROP5) expressed by the protozoan parasite, Toxoplasma gondii. Mouse IRGs are encoded by an extensive and rapidly evolving family of over 20 genes. Similarly, the ROP5 family is highly polymorphic and consists of 4-10 genes, depending on the strain of Toxoplasma. IRGs are known to be avidly bound and functionally inactivated by ROP5 proteins, but the molecular basis of this interaction/inactivation has not previously been known. Here we show that ROP5 uses a highly polymorphic surface to bind adjacent to the nucleotide-binding domain of an IRG and that this produces a profound allosteric change in the IRG structure. This has two dramatic effects: 1) it prevents oligomerization of the IRG, and 2) it alters the orientation of two threonine residues that are targeted by the Toxoplasma Ser/Thr kinases, ROP17 and ROP18. ROP5s are highly specific in the IRGs that they will bind, and the fact that it is the most highly polymorphic surface of ROP5 that binds the IRG strongly supports the notion that these two protein families are co-evolving in a way predicted by the Red Queen hypothesis.

Indexed as

Allosteric RegulationAnimalsGTP PhosphohydrolasesHost-Parasite InteractionsHumansMiceModels, MolecularPhosphotransferasesProtozoan ProteinsToxoplasmaToxoplasmosisGTP PhosphohydrolasesIigp1 protein, mousePhosphotransferasesProtozoan ProteinsCrystal StructureGTPaseInnate ImmunityParasitologyProtein Kinase

Identifiers

PMID25118287
PMCPMC4183819

What OpenQuestion holds

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Registered trials

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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.