通过LptB2FGC复合物提取脂多糖的结构基础
Yanyan Li1, Benjamin J Orlando1, Maofu Liao2
1Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Nature
|March 22, 2019
概括
已经揭示了脂多糖转运 (Lpt) 复合物LptB2FGC的结构,这种复合物对格拉姆阴性细菌至关重要. 其他:
科学领域:
- 微生物学
- 结构生物学
- 生物化学
背景情况:
- 脂多糖 (LPS) 对于格拉姆阴性细菌的外膜完整性和抗生素耐药性至关重要.
- 由LptA-G蛋白组成的脂多糖转运系统 (Lpt) 促进LPS从内膜转移到外膜.
- 与LptC相关的ATP绑定磁带输送器LptB2FG是从内膜提取LPS的关键,但其机制和LptC的作用尚不清楚.
研究的目的:
- 阐明LptB2FG-LptC复合体 (LptB2FGC) 在脂多糖转运中的结构机制.
- 了解LptC在调节ATP结合盒传送器LptB2FG中的作用.
- 揭示LptB2FGC复合物和脂多糖之间的详细相互作用.
主要方法:
- 使用单粒子冷电子显微镜 (cryo-EM) 来确定LptB2FG和LptB2FGC的结构.
- 结构在无核酸和无酸陷入状态下被解析,以捕获不同的功能构造.
- 对冷-EM结构的详细分析确定了结合的脂多糖和蛋白质-脂质相互作用.
主要成果:
- 通过可视化结合的脂多糖,获得了LptB2FG和LptB2FGC的高分辨率冷EM结构.
- 这些结构揭示了载体和脂多糖之间的细节链相互作用,解释了捕获和挤出机制.
- 发现LptC将其跨膜螺旋体插入LptB2FG,这是ABC传送器的一种新型调节机制,将LPS传输与结构变化相合.
结论:
- LptB2FGC结构提供了前所未有的洞察力,了解细菌内膜中脂多糖转移的机制.
- LptC通过调节LptB2FG活性,并可能协调周周等离子体Lpt蛋白相互作用,起到关键的调节作用.
- 了解这种复合物对于开发抗生素耐药性的新方法至关重要.
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