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冠状病毒肺炎效应体SemD通过结构和功能模仿利用其宿主的内细胞机器
Fabienne Kocher1, Violetta Applegate2, Jens Reiners2
1Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute for Functional Microbial Genomics, Düsseldorf, Germany.
Nature communications
|August 24, 2024
概括
冠状病毒肺炎使用其SemD效应蛋白来劫持宿主细胞的入口. SemD与N-WASP结合,激活了动氨酸细胞骨架,并促进了病原体的内部化.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 冠状病毒肺炎是一种强制性的细胞内病原体,侵入宿主上皮细胞.
- 病原体的进入依赖于分泌的效应蛋白,这些蛋白操纵宿主细胞机械,特别是内细胞分裂.
研究的目的:
- 为了阐明 Chlamydia pneumoniae 效应体 SemD 与宿主细胞蛋白质相互作用的结构基础.
- 了解SEMD如何促进病原体进入宿主细胞的内化.
主要方法:
- 通过与宿主结合伙伴共同结晶来对SemD进行高分辨率的结构确定.
- 对SemD的绑定相互作用和域灵活性进行分析.
主要成果:
- 通过选择Cdc42结合部位,SemD结合并激活宿主活性调节剂N-WASP,从而绕过了对活性Cdc42的需求.
- SemD表现出特异性,强烈结合N-WASP,但不结合FMNL2.
- SemD具有灵活和结构化的域,可以与宿主细胞膜,SNX9和N-WASP同时相互作用.
结论:
- 通过与宿主蛋白质的特定相互作用,SemD在结构上劫持了宿主内细胞系统.
- 这种机制使克拉米迪亚肺炎能够有效地被内化到上皮细胞中.
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