通过ATP结合,可以从多药性蛋白1中释放基质
Zachary Lee Johnson1, Jue Chen1
1Laboratory of Membrane Biology and Biophysics, The Rockefeller University and Howard Hughes Medical Institute, New York, NY 10065, USA.
Cell
|January 2, 2018
概括
多种药物耐药性蛋白MRP1使用ATP将化疗药物出细胞. 在使用ATP之前释放药物,完成运输周期.
科学领域:
- 生物化学
- 分子生物学
- 结构生物学
背景情况:
- 多种药物耐药性蛋白1 (MRP1) 是一种ATP结合盒 (ABC) 载体.
- 通过从细胞中挤出药物,使MRP1对化疗产生耐药性.
- 之前的研究表明基质向内面的结合部位招募.
研究的目的:
- 通过MRP1阐明高亲和度基质穿过膜的机制.
- 描述由MRP1释放的基质所涉及的形状变化.
主要方法:
- 使用电子低温显微镜 (cryo-EM) 可视化MRP1.
- 在不同形态状态下对MRP1进行结构分析.
主要成果:
- 通过ATP结合重新配置基质结合部位,从而降低其亲和力.
- 在ATP结合时,运输途径向细胞外空间开放.
- 在ATP水解之前发生基质释放.
结论:
- 现在描述了由MRP1进行基质运输的完整构造周期.
- 了解这种循环对于开发克服多种药物耐药性的策略至关重要.
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