2. Academic Validation
  3. Bacterial effector restricts liquid-liquid phase separation of ZPR1 to antagonize host UPRER

Bacterial effector restricts liquid-liquid phase separation of ZPR1 to antagonize host UPRER

  • Cell Rep. 2023 Jun 27;42(7):112700. doi: 10.1016/j.celrep.2023.112700.
Xiaoxiao Ouyang 1,  Xueyun Wang 1,  Pan Li 1,  Qin Huang 1,  Li Zhou 1,  Jingxiang Li 1,  Li Gao 2,  Qi Sun 1,  Fangni Chai 1,  Shupan Guo 1,  Zhihui Zhou 1,  Xin Liu 1,  Lunzhi Dai 2,  Wei Cheng 3,  Haiyan Ren 4
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • 2 Department of General Practice and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, and Sichuan University, Chengdu 610041, China.
  • 3 Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Collaborative Innovation Center of Biotherapy, Sichuan University West China Hospital, Chengdu, Sichuan 610041, China.
  • 4 Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Collaborative Innovation Center of Biotherapy, Sichuan University West China Hospital, Chengdu, Sichuan 610041, China. Electronic address: [email protected].
PMID: 37379216 DOI: 10.1016/j.celrep.2023.112700
Abstract

How pathogens manipulate host UPRER to mediate immune evasion is largely unknown. Here, we identify the host zinc finger protein ZPR1 as an interacting partner of the enteropathogenic E. coli (EPEC) effector NleE using proximity-enabled protein crosslinking. We show that ZPR1 assembles via liquid-liquid phase separation (LLPS) in vitro and regulates CHOP-mediated UPRER at the transcriptional level. Interestingly, in vitro studies show that the ZPR1 binding ability with K63-ubiquitin chains, which promotes LLPS of ZPR1, is disrupted by NleE. Further analyses indicate that EPEC restricts host UPRER pathways at the transcription level in a NleE-ZPR1 cascade-dependent manner. Together, our study reveals the mechanism by which EPEC interferes with CHOP-UPRER via regulating ZPR1 to help pathogens escape host defense.

Keywords

CP: Microbiology; UPR(ER); liquid-liquid phase separation; pathogen-host interaction; proximity enabled protein crosslinking; unnatural amino acids.

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