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通过Arf1招募和激活AP-1克拉林适配器复合物的结构基础
Xuefeng Ren1, Ginny G Farías, Bertram J Canagarajah
1Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|February 19, 2013
概括
适应蛋白1 (AP-1) 复合体对于细胞内货物分类至关重要,由Arf1-GTP.激活. 结构和生物化学数据揭示了Arf1如何解锁AP-1,从而使货物结合和运输.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 结构生物学是结构生物学.
背景情况:
- 适配蛋白1 (AP-1) 复合体介导跨戈尔吉网络和内分泌体之间的货物分类.
- 将AP-1招募到细胞区的过程取决于GTPase Arf1.1.
研究的目的:
- 阐明Arf1-GTP介导AP-1激活的结构和机制基础.
- 了解Arf1绑定如何解锁AP-1进行货物识别.
主要方法:
- AP-1-Arf1-GTP复合物的X射线晶体学.
- 蛋白质与蛋白质相互作用的生物化学分析.
主要成果:
- 晶体结构显示Arf1-GTP与两个AP-1复合体结合,将它们连接到不同的位置.
- Arf1-GTP与AP-1的β1和γ子单元相互作用,诱导货物结合的"解锁"状态.
- 在g亚单元上的第三个Arf1相互作用位点对于AP-1的招募而不是激活至关重要.
结论:
- Arf1-GTP充当分子开关,通过诱导有利于货物结合的结构变化来激活AP-1.
- 建议Arf1对AP-1的招募和激活进行详细的模型,整合结构和功能数据.
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