Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I.
Okuma, H.; Saijo-Hamano, Y.; Sherif, A. A.; Hoshizaki, E.; Sakai, N.; Kato, T.; Imasaki, T.; Nitta, E.; Sasai, M.; Maniwa, Y.; Kosako, H.; Standley, D. M.; Yamamoto, M.; Nitta, R.
Show abstract
Upon infection with Toxoplasma gondii, host cells produce immune-related GTPases (IRGs) to kill the parasite. T. gondii counters this response by releasing ROP18 kinase, which inactivates IRG GTPases and inhibits their recruitment to the T. gondii parasitophorous vacuole (PV). However, the molecular mechanisms of this process are entirely unknown. Here we report the atomic structures of Irgb6 with a phosphomimetic mutation by ROP18. The mutant has lower GTPase activity and is not recruited to the PV membrane (PVM). The crystal structure shows the mutant exhibit a distinct conformation from the physiological nucleotide-free form, thus preventing GTPase cycling. This change allosterically modifies the conformation of the membrane-binding interface, preventing physiological PVM-binding. Docking simulation of PI5P also supports the impaired binding of the mutant to PVM. We thus demonstrate the structural basis for T. gondii escape from host cell-autonomous defense, and provide a structural model for regulating enzymatic activity by phosphorylation.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Structural and functional studies of the first tripartite protein complex at the Trypanosoma brucei flagellar pocket collar 94%
- Bartonella effector protein C mediates actin stress fiber formation via recruitment of GEF-H1 to the plasma membrane 94%
- DNA replication protein Cdc45 directly interacts with PCNA via its PIP box in Leishmania donovani and the Cdc45 PIP box is essential for cell survival 93%
Similar papers in this journal
- An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation in Trypanosoma brucei 94%
- Structural and regulatory insights into the glideosome-associated connector from Toxoplasma gondii 94%
- Disease related mutations in PI3Kγ disrupt regulatory C-terminal dynamics and reveals a path to selective inhibitors 94%
Similar papers in this journal
Similar papers in this journal
- Molecular basis for Ras suppressor-1 recruitment to focal adhesions and stabilization of consensus adhesome complex 94%
- Structure of transmembrane prolyl 4-hydroxylase reveals unique organization of EF and dioxygenase domains 94%
- A Legionella effector kinase is activated by host inositol hexakisphosphate 93%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.