Abstract
Author Summary Toxoplasma gondii is an intracellular parasitic protozoan infecting about a third of humankind. Humans, however, are unlikely to be important hosts in terms of the evolution of the parasite because, for completion of the parasite sexual cycle, the infected animal must be eaten by a cat. Therefore, important intermediate hosts for Toxoplasma are species like mice that are often preyed on by cats. Mice use an intracellular resistance mechanism, the IRG proteins, against Toxoplasma. In turn, Toxoplasma appears to have evolved a virulence factor, a protein kinase called ROP18, that inactivates IRG proteins. We show that ROP18 does not act alone. It needs help from the ROP5 pseudokinases, proteins related to ROP18 but without enzymatic activity. ROP5 pseudokinases assist ROP18 by binding to the IRG proteins, holding them inactive, and laying them open to enzymatic attack and likely permanent inactivation by the ROP18 kinase. This mechanism illustrates the principle that members of an enzyme family can lose their enzymatic activity and evolve into regulators or co-factors for the active members.
Highlights
Toxoplasma gondii (T. gondii) is an intracellular parasitic protozoan of the phylum Apicomplexa, a relative of the malarial Plasmodia
Toxoplasma gondii is an intracellular parasitic protozoan infecting about a third of humankind
Irga6 Binds T. gondii-Derived ROP5 in Vitro To identify T. gondii proteins interacting with IRG proteins, we prepared Glutathione Sepharose 4B beads loaded with glutathione S-transferase (GST)-Irga6 to pull down proteins from detergent lysates of IFNc-induced L929 fibroblasts that had been infected 2 h earlier with the virulent T. gondii type I strain, RHYFP
Summary
Toxoplasma gondii (T. gondii) is an intracellular parasitic protozoan of the phylum Apicomplexa, a relative of the malarial Plasmodia. While T. gondii strains of the types II and III clonal lineages are largely avirulent, strains of the type I clonal lineage are highly virulent [2], killing immunologically competent but naıve hosts within 10 d [3]. It has been known for many years that interferon-c (IFNc) is essential for resistance against T. gondii [4]. A previously underexplored family of IFNc-inducible large GTPases, the IRG proteins (formerly the p47 GTPases), has been shown to carry much of the responsibility for the successful early resistance of mice to avirulent T. gondii strains [5,6]. IRG protein accumulation disrupts the integrity of the PVM [12,14,15] and the enclosed parasite is killed for unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
