细菌效应物限制 ZPR1 的液-液相分离以拮抗宿主 UPR。
Bacterial effector restricts liquid-liquid phase separation of ZPR1 to antagonize host UPR.
机构信息
Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
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.
出版信息
Cell Rep. 2023 Jul 25;42(7):112700. doi: 10.1016/j.celrep.2023.112700. Epub 2023 Jun 27.
How pathogens manipulate host UPR 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 UPR 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 UPR pathways at the transcription level in a NleE-ZPR1 cascade-dependent manner. Together, our study reveals the mechanism by which EPEC interferes with CHOP-UPR via regulating ZPR1 to help pathogens escape host defense.
宿主 UPR 如何被病原体操纵以介导免疫逃避在很大程度上尚不清楚。在这里，我们使用邻近连接蛋白交联技术鉴定了宿主锌指蛋白 ZPR1 是肠致病性大肠杆菌（EPEC）效应蛋白 NleE 的相互作用伙伴。我们发现 ZPR1 在体外通过液-液相分离（LLPS）组装，并在转录水平上调节 CHOP 介导的 UPR。有趣的是，体外研究表明，ZPR1 与 K63-泛素链的结合能力，促进了 ZPR1 的 LLPS，被 NleE 破坏。进一步的分析表明，EPEC 以一种依赖于 NleE-ZPR1 级联的方式在转录水平上限制宿主 UPR 途径。总之，我们的研究揭示了 EPEC 通过调节 ZPR1 干扰 CHOP-UPR 的机制，帮助病原体逃避宿主防御。
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