Genetically incorporated crosslinkers reveal NleE attenuates host autophagy dependent on PSMD10
| Autor: | Pan Li, Li Zhou, Qi Sun, Zhihui Zhou, Jingxiang Li, Wei Cheng, Fangni Chai, Lunzhi Dai, Shiqian Qi, Xiaoxiao Ouyang, Li Gao, Shupan Guo, Haiyan Ren, Kefeng Lu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Models Molecular 0301 basic medicine Proteasome Endopeptidase Complex autophagy QH301-705.5 Protein Conformation Virulence Factors Science Chemical biology Virulence Autophagy-Related Protein 7 01 natural sciences General Biochemistry Genetics and Molecular Biology ATG12 Enteropathogenic Escherichia coli 03 medical and health sciences Biochemistry and Chemical Biology Proto-Oncogene Proteins Humans Protein Interaction Domains and Motifs unnatural amino acid Biology (General) Escherichia coli Infections Innate immune system General Immunology and Microbiology Interleukin-6 010405 organic chemistry Chemistry Effector Escherichia coli Proteins General Neuroscience Autophagy Cell Biology General Medicine 0104 chemical sciences Cell biology 030104 developmental biology Proteasome covalent crosslinking Medicine PSMD10 Autophagy-Related Protein 12 HeLa Cells Research Article Human |
| Zdroj: | eLife eLife, Vol 10 (2021) |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.69047 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|