MsbA介导的脂多糖转移的结构基础
Wei Mi1, Yanyan Li2, Sung Hwan Yoon3
1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|September 5, 2017
概括
研究人员揭示了MsbA作为一种必不可少的输送物如何将脂多糖 (LPS) 转移到细菌膜的结构基础. 这为细菌细胞包装和潜在的药物点提供了新的见解.
科学领域:
- 生物化学
- 结构生物学
- 微生物学
背景情况:
- 脂聚糖 (LPS) 是格拉姆阴性细菌外膜的关键组成部分.
- MsbA是一种ATP结合的磁带载体,负责将LPS从内膜传单转移到外膜传单.
- 通过MsbA进行的LPS运输的结构机制尚不清楚.
研究的目的:
- 阐明MsbA驱动的LPS翻转背后的结构机制.
- 在不同功能状态下确定 MsbA 的结构.
- 了解MSBA对LPS的认可和约束力
主要方法:
- 单粒子冷电子显微镜 (冷EM).
- MsbA的脂质纳米盘复制
- 在无核酸,ADP-瓦纳酸结合和ADP-结合状态下确定MsbA结构.
主要成果:
- 在三种不同的功能状态下获得了MsbA的高分辨率冷EM结构.
- 发现LPS在MsbA的深层结合,与水友和疏水性残留物相互作用.
- 在LPS运输过程中,向外,向内和封闭形状之间的 MsbA 过渡.
结论:
- 这项研究揭示了LPS的约束性和认可的结构性基础.
- 在MsbA的形状变化对于LPS在内膜上翻转至关重要.
- 这些发现为了解其他脂质翻酶和开发新型抗菌策略提供了基础.
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