A Bifunctional T3SS-Effector Simultaneously Cleaves Host MAP Kinase and Inhibits PPM1A Phosphatase - PubMed

5 hours ago

NleD, a metalloprotease and T3SS effector, inactivates host p38 and JNK MAP kinases by cleaving them within the TXY motif.
NleD also binds to and inhibits the host metallophosphatase PPM1A, blocking its catalytic pocket while retaining its own proteolytic function.
Structural analysis shows NleD blocks phospho-protein substrate access to PPM1A's catalytic site, suppressing its phosphatase activity.
In a Citrobacter rodentium murine model, NleD enhances intestinal colonization independently of its protease activity, likely via PPM1A interaction.
NleD is identified as a bifunctional effector, demonstrating sophisticated manipulation of host signaling pathways by T3SS effectors.

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