Genetically incorporated crosslinkers reveal NleE attenuates host autophagy dependent on PSMD10
- Sichuan University, China
Abstract
Autophagy acts as a pivotal innate immune response against infection. Some virulence effectors subvert the host autophagic machinery to escape the surveillance of autophagy. The mechanism by which pathogens interact with host autophagy remains mostly unclear. However, traditional strategies often have difficulty identifying host proteins that interact with effectors due to the weak, dynamic and transient nature of these interactions. Here, we found that Enteropathogenic Escherichia coli (EPEC) regulates autophagosome formation in host cells dependent on effector NleE. The 26S Proteasome Regulatory Subunit 10 (PSMD10) was identified as a direct interaction partner of NleE in living cells by employing genetically incorporated crosslinkers. Pairwise chemical crosslinking revealed that NleE interacts with the N-terminus of PSMD10. We demonstrated that PSMD10 homodimerization is necessary for its interaction with ATG7 and promotion of autophagy, but not necessary for PSMD10 interaction with ATG12. Therefore, NleE-mediated PSMD10 in monomeric state attenuates host autophagosome formation. Our study reveals the mechanism through which EPEC attenuates host autophagy activity.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Key Research and Development Program of China (2018YFC1002802)
- Haiyan Ren
National Key Research and Development Program of China (2018YFA0109200)
- Haiyan Ren
National Natural Science Foundation of China (31872727)
- Haiyan Ren
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Genetically incorporated crosslinkers reveal NleE attenuates host autophagy dependent on PSMD10
eLife 10:e69047.
https://doi.org/10.7554/eLife.69047
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