细菌膜蛋白TolC的晶体结构是多药物排放和蛋白质出口的中心
V Koronakis1, A Sharff, E Koronakis
1Department of Pathology, University of Cambridge, UK.
Nature
|July 6, 2000
概括
格拉姆阴性细菌通过TolC蛋白质输出各种分子. 晶体结构揭示了由三个TolC单元形成的独特通道道,解释了细菌排泄机制.
科学领域:
- 结构生物学 结构生物学
- 微生物学 微生物学
- 生物化学 生物化学
背景情况:
- 格拉姆阴性细菌具有复杂的细胞外,内外膜.
- 通过两种膜有效地运输各种分子对于细菌的生存和功能至关重要.
- 托尔C蛋白家族参与各种基质的直接出口,绕过周等离子体.
研究的目的:
- 为了确定来自大肠杆菌的TolC外膜蛋白的高分辨率晶体结构.
- 阐明通过细菌细胞膜形成连续输出管道的结构基础.
- 提出一个 TolC 介导的基板运输机制及其调节.
主要方法:
- 在2.1-Å分辨率的X射线晶体学.
- 对TolC的三维结构的分析.
- 结构比较分析和机制建模.
主要成果:
- 大肠杆菌TolC的晶体结构揭示了一个新的蛋白质折叠.
- 三个TolC原体组装成一个连续的,溶剂可访问的通道道,跨越140 Å.
- 道的近端被卷轴螺旋封闭,这表明道开放的调节机制.
结论:
- TolC结构为直接出口通过两个细菌膜提供了一个分子解释.
- 为细菌排泄提出了一种涉及TolC通道全性开放的一般机制.
- 这一发现推动了我们对细菌耐药性和毒性机制的理解.
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