一个ABC载体与其结合蛋白质复合体中的结构
Kaspar Hollenstein1, Dominik C Frei, Kaspar P Locher
1Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland.
Nature
|February 27, 2007
概括
研究人员可视化了酸盐输送器ModB2C2A,揭示了其向内转向的形状. 与ABC出口商相比,这种结构表明营养吸收和药物排放的共同交替接入机制.
科学领域:
- 结构生物学 结构生物学
- 生物化学 生物化学
- 运输的分子机制的运输.
背景情况:
- ATP结合盒 (ABC) 载体是关键的膜蛋白,参与营养吸收和药物耐药性.
- 细菌ABC进口者对于营养获取至关重要,而ABC出口者可以在癌症中引起多药性耐药性.
- 需要高分辨率的结构来理解ABC传送器的不同形状和机制.
研究的目的:
- 确定与其结合蛋白 (ModA) 复合的Archaeoglobus fulgidus 酸盐转运体 (ModB2C2) 的高分辨率晶体结构.
- 阐明ABC进口商中基质转移的结构基础.
- 为了比较ModB2C2A的机制与已知的ABC出口商,如Sav1866.
主要方法:
- 进行X射线晶体学,以获得ModB2C2A复合体的3.1 Å分辨率结构.
- 跨膜域 (ModB) 和核酸结合域 (ModC) 的结构分析.
- 与多药ABC出口商Sav1866.6进行比较结构分析.
主要成果:
- ModB2C2A结构揭示了带有闭门的跨膜螺旋体 (ModB) 的面向内部的构造.
- 核酸结合域 (ModC) 处于一个无核酸的开放形状.
- 结合蛋白 (ModA) 将基质结合裂定位到输送器的内部通路.
结论:
- ModB2C2A结构为细菌ABC进口者吸收营养的机制提供了洞察力.
- 与Sav1866的结构比较表明,对于进口商和出口商来说,保留了交替访问和释放机制.
- ATP结合可能会驱动面向外的形状,而水解产物解离则有利于面向内的形状.
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