在检测到髓暴露时,TECPR1将LC3与受损的内膜结合起来
Keith B Boyle1, Cara J Ellison1, Paul R Elliott1
1Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
The EMBO journal
|July 6, 2023
概括
宿主细胞使用TECPR1来检测细菌斯芬哥米林,TECPR1是一种启动抗菌自的新型受体. 这一发现揭示了感知细胞内细菌危险信号的新途径.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 侵入性细菌会在真空细胞破裂时向宿主细胞细胞醇暴露诸如甘氨酸和斯芬戈米林等危险信号.
- 盖莱克-8识别了甘氨酸,触发了自,但对细胞结合物斯芬戈米林的感知机制尚不清楚.
研究的目的:
- 为了识别负责检测细胞结合物菌素的宿主细胞受体.
- 阐明斯芬戈米林触发抗菌反应的分子机制.
主要方法:
- 蛋白相互作用研究以确定TECPR1作为基米林受体.
- 生物化学试验以表征TECPR1-sphingomyelin相互作用.
- 测定TECPR1 N端域 (N'DysF) 的晶体结构.
- 功能性测试以评估LC3脂化和自诱导.
主要成果:
- TECPR1作为受体作用于细胞溶液暴露的基肌蛋白.
- TECPR1招募ATG5,形成一个E3结合酶复合体,调解LC3脂质结合.
- TECPR1的N端DysF域通过关键残留物,如W154,特别结合基林.
- TECPR1的功能与ATG16L1相似,它赋予ATG5/ATG12 E3结合酶的特异性.
结论:
- TECPR1是一种新型的基肌蛋白传感器,可启动抗菌自途径.
- 这些发现揭示了对细胞内细菌病原体的宿主防御的替代机制.
- TECPR1独特的DysF域及其在E3结合酶特异性中的作用扩大了我们对细胞先天免疫的理解.
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