Genetically incorporated crosslinkers reveal NleE attenuates host autophagy dependent on PSMD10

Autor: Jingxiang Li, Shupan Guo, Fangni Chai, Qi Sun, Pan Li, Li Gao, Lunzhi Dai, Xiaoxiao Ouyang, Zhihui Zhou, Li Zhou, Wei Cheng, Shiqian Qi, Kefeng Lu, Haiyan Ren
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: eLife, Vol 10 (2021)
Druh dokumentu: article
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: Directory of Open Access Journals