保存的域间相互作用推动了跨戈尔吉网络的局部化和同类铜ATP酶的贩运
Sharon Mary Jose1, Saptarshi Maji1, Mrittika Paul1
1Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal 741246, India.
Journal of cell science
|December 18, 2025
概括
铜ATPases调节细胞中的铜运输. 这些蛋白质内部的域相互作用对于铜诱导的贩运至关重要,进化分歧会影响功能.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 分子进化分子进化
背景情况:
- 多型铜ATPases (ATP7A和ATP7B) 对于细胞铜恒温至关重要.
- 这些蛋白质在跨戈尔吉网络 (TGN) 和血膜之间进行流通,以管理铜水平.
研究的目的:
- 调查驱动铜-ATPase贩运的域间相互作用.
- 确定ATP7A和ATP7B的同源域之间的进化差异.
主要方法:
- 在ATP7A和ATP7B之间通过交换域 (氨基终端 (NT),核酸结合 (NBD),C终端) 创建了仿真铜-ATPase.
- 评估了化学蛋白质的贩运表型.
- 对NT-NBD相互作用进行了体外结合研究.
- 分析了正确的铜-ATPase域的进化关系.
主要成果:
- 化学ATP7B蛋白显示出不同的贩运模式.
- ATP7B与替代的NT被构成性地运输到底侧膜.
- 同时在ATP7B中替换NT-NBD导致TGN局部化,这表明NT-NBD相互作用对TGN保留至关重要.
- 相互替代ATP7A并没有恢复膜局部,这表明域不相容和ATP7B域分歧.
- 序列分析揭示了NT和NBD域在物种间的共同进化.
结论:
- 铜-ATPases对铜的反应性贩运与其域上的进化约束有关.
- 域相互作用,特别是NT和NBD之间的相互作用,对于适当的TGN定位和铜流量调节至关重要.
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