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

Xiaoxiao Ouyang; Xueyun Wang; Pan Li; Qin Huang; Li Zhou; Jingxiang Li; Li Gao; Qi Sun; Fangni Chai; Shupan Guo; Zhihui Zhou; Xin Liu; Lunzhi Dai; Wei Cheng; Haiyan Ren

Cell Reports (Jul 2023)

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

Xiaoxiao Ouyang,
Xueyun Wang,
Pan Li,
Qin Huang,
Li Zhou,
Jingxiang Li,
Li Gao,
Qi Sun,
Fangni Chai,
Shupan Guo,
Zhihui Zhou,
Xin Liu,
Lunzhi Dai,
Wei Cheng,
Haiyan Ren

Affiliations

Xiaoxiao Ouyang: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Xueyun Wang: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Pan Li: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Qin Huang: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Li Zhou: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Jingxiang Li: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Li Gao: 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
Qi Sun: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Fangni Chai: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Shupan Guo: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Zhihui Zhou: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Xin Liu: Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Lunzhi Dai: 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
Wei Cheng: 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
Haiyan Ren: 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; Corresponding author

Journal volume & issue: Vol. 42, no. 7
p. 112700

Abstract

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Summary: 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.

CP: Microbiology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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