TY - JOUR TI - Genetically incorporated crosslinkers reveal NleE attenuates host autophagy dependent on PSMD10 AU - Li, Jingxiang AU - Guo, Shupan AU - Chai, Fangni AU - Sun, Qi AU - Li, Pan AU - Gao, Li AU - Dai, Lunzhi AU - Ouyang, Xiaoxiao AU - Zhou, Zhihui AU - Zhou, Li AU - Cheng, Wei AU - Qi, Shiqian AU - Lu, Kefeng AU - Ren, Haiyan A2 - Dikic, Ivan A2 - Soldati-Favre, Dominique A2 - Dikic, Ivan VL - 10 PY - 2021 DA - 2021/07/13 SP - e69047 C1 - eLife 2021;10:e69047 DO - 10.7554/eLife.69047 UR - https://doi.org/10.7554/eLife.69047 AB - 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. KW - autophagy KW - unnatural amino acid KW - covalent crosslinking JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -