细菌效应器限制ZPR1的液-液相分离,以对抗宿主UPRER
Xiaoxiao Ouyang1, Xueyun Wang1, Pan Li1
1Department of Pulmonary and Critical Care, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Cell reports
|June 28, 2023
概括
肠道病原性大肠杆菌 (EPEC) 使用NleE效应器通过向ZPR1蛋白来破坏展开的蛋白质反应 (UPRER),帮助病原体免疫逃避.
科学领域:
- 细胞生物学 细胞生物学
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
背景情况:
- 病原体对宿主细胞通路的操纵对于免疫逃避至关重要.
- 展开的蛋白质反应 (UPRER) 是一个关键的细胞防御机制.
- 诸如肠病原性大肠杆菌 (EPEC) 等病原体逃避UPRER的机制尚未完全理解.
研究的目的:
- 调查EPEC如何操纵宿主UPRER以逃避免疫.
- 为了确定参与EPEC与UPRER的干扰的宿主因素.
- 为了阐明EPEC介导的UPRER调节的分子机制.
主要方法:
- 启用近距离的蛋白质交叉链接以识别EPEC效应器相互作用伙伴.
- 在体外研究评估ZPR1蛋白的行为,包括液态液相分离 (LLPS).
- 转录分析以评估UPRER通路的调节.
主要成果:
- 主体指蛋白ZPR1被确定为EPEC效应器NleE的相互作用伙伴.
- 在体外,ZPR1经历液-液相分离 (LLPS),并调节CHOP介导的UPRER转录.
- EPEC的NleE效应器破坏了ZPR1与K63-ubiquitin链的结合,从而抑制了ZPR1的LLPS.
- 通过NleE-ZPR1级联,EPEC通过转录来限制宿主UPRER途径.
结论:
- 通过向ZPR1.1,EPEC干扰了CHOP-UPRER通路,从而影响了ZPR1.
- NleE-ZPR1相互作用和随后的ZPR1LLPS破坏是病原体免疫逃避的一个新机制.
- 了解这种相互作用可以了解宿主-病原体动态和潜在的治疗点.
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