需要EMC来启动精确的膜蛋白拓生
Patrick J Chitwood1, Szymon Juszkiewicz1, Alina Guna1
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Cell
|November 13, 2018
概括
ER膜蛋白复合体 (EMC) 对于正确插入许多膜蛋白的第一个跨膜域 (TMD) 至关重要,包括G蛋白合受体 (GPCR). 这保证了蛋白质的适当生物生成和功能.
科学领域:
- 分子生物学
- 细胞生物学
- 生物化学
背景情况:
- 哺乳动物可以合成大约5000个完整的膜蛋白.
- 这些蛋白质进入内质网膜 (ER) 的插入机制尚未完全理解.
- 精确的拓插入对于蛋白质功能至关重要.
研究的目的:
- 研究ER膜蛋白复合体 (EMC) 在整体膜蛋白的生物发生中的作用.
- 阐明EMC促进蛋白质插入ER膜的具体机制.
- 了解EMC和其他蛋白质转位机制之间的相互作用.
主要方法:
- 使用β1上腺素受体 (β1AR) 生成的复制研究.
- 使用纯化的EMC和SRP受体进行体外插入测试.
- 在EMC淘汰细胞中分析GPCR生物发生.
- 使用N端信号对蛋白质拓进行操纵.
主要成果:
- 需要EMC才能有效地产生β1AR和其他GPCR.
- 对于第一个跨膜域 (TMD1) 的共翻译插入,特别需要EMC.
- 没有EMC,TMD1的插入可能会逆转或失败,而Sec61转位器则介导后续TMD的插入.
- 通过N端信号绕过EMC要求,恢复了EMC淘汰细胞中的GPCR生物发生.
结论:
- 在膜蛋白生物生成过程中,EMC在确保TMDs正确的同翻译插入方面发挥着至关重要的作用.
- EMC与Sec61转位子合作,以实现许多膜蛋白的精确拓.
- 了解EMC功能是解读膜蛋白插入复杂过程的关键.
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