Related Experiment Video
Updated: Mar 29, 2026
10:17
A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
Published on: April 29, 2022
3.0K
A Bifunctional T3SS-Effector Simultaneously Cleaves Host MAP Kinase and Inhibits PPM1A Phosphatase
Yaakov Socol1, Lihi Gur-Arie1, Netanel Tzarum2
1Department of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 28, 2026
Summary
Enteropathogenic E. coli
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- NleD is a metalloprotease and Type III secretion system (T3SS) effector.
- NleD inactivates p38 and JNK MAP kinases by cleaving the TXY motif.
Purpose of the Study:
- Investigate NleD's interaction with host metallophosphatase PPM1A.
- Determine the mechanism of NleD-PPM1A interaction and its functional consequences.
Main Methods:
- Co-immunoprecipitation assays to study protein interactions.
- Enzyme activity assays to measure protease and phosphatase activity.
- Structural analysis of the NleD-PPM1A complex.
- Murine infection model using Citrobacter rodentium.
Main Results:
- NleD binds to PPM1A, inhibiting its phosphatase activity while retaining its own proteolytic function.
- Structural data shows NleD blocks substrate access to PPM1A's catalytic pocket.
- NleD enhances intestinal colonization in vivo independently of protease activity, potentially via PPM1A interaction.
Conclusions:
- NleD is a bifunctional effector with both protease and PPM1A inhibitory activities.
- NleD manipulates host signaling pathways through sophisticated T3SS effector strategies.
- NleD's interaction with PPM1A contributes to pathogen colonization.
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