膜组装了一个MAN1B1-VCP复合体,以向从内质网膜到溶酶体的外来糖蛋白,以降解
Jing Zhang1, Xiaoran Lu1, Sunan Li1
1State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 1, 2025
概括
门布拉林是一种新的ER-phagy受体,通过独特的途径向病毒葡萄糖蛋白进行溶酶体降解,增强先天的抗病毒防御能力. 这一过程将异物从宿主蛋白质中区分开来,独立于无处不在.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
背景情况:
- 细胞内膜网膜 (ER) 蛋白质质量控制通过与ER相关的降解 (ERAD) 和与ER相结合的降解 (ERLAD) 维持蛋白质稳定.
- 选择性自受体在向特定基质进行降解方面发挥着至关重要的作用.
研究的目的:
- 确定参与蛋白质质量控制的新型ER-phagy受体.
- 阐明ER区分外来和宿主糖蛋白进行降解的机制.
- 调查 Membralin 在先天性抗病毒防御中的作用.
主要方法:
- 酵母二杂交查和共免疫沉以确定相互作用的蛋白质.
- 基因编辑CRISPR/Cas9以产生淘汰细胞系.
- 焦显微镜和西方涂抹分析蛋白质局部化和降解.
- 伪病毒感染性测定用于评估抗病毒功能.
主要成果:
- 识别了membralin (TMEM259) 作为一种新型ER-phagy受体,可以吸引MAN1B1和VCP/p97.
- 门布拉林-MAN1B1-VCP复合物中介于病毒葡萄糖蛋白 (SARS-CoV-2尖端,埃博拉GP,流感HA,HIV-1Env) 的降解,而不依赖于多比基因化.
- 这种途径选择性地向病毒葡萄糖蛋白,使其与传统ERAD或FAM134B依赖ERLAD降解的错误折叠宿主葡萄糖蛋白区别开来.
- 丢失Membralin或MAN1B1会增加伪病毒感染力,突出显示Membralin的抗病毒作用.
结论:
- 膜作为一个至关重要的支架,用于无素独立的ER-to-lysosome相关降解途径.
- 这一途径通过选择性降解外来病毒葡萄糖蛋白来提供先天的抗病毒防御.
- 薄膜蛋白协调ER质量控制与天生的免疫力,为抗病毒策略提供了一个新的目标.
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