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一个完整的Bce型抗微生物抗性模块的架构
Natasha L George1,2, Benjamin J Orlando3
1Dept. of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Nature communications
|July 1, 2023
概括
阳性细菌使用Bce模块来感知和抵抗抗微生物. 这项研究揭示了这些复合物的结构,揭示了新的组装机制和核酸结合激活过程.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 格拉姆阳性细菌产生针对酸糖合成的抗菌.
- 细菌耐药结节分裂 (Bnd) 家族蛋白质,包括ABC载体和传感器蛋白质,介导耐药性.
- 由Bce型ABC转运器和传感器histidine kinase组成的Bce模块对于感知和抵抗抗菌来说至关重要.
研究的目的:
- 阐明Bce模块组装和功能的结构基础.
- 为ABC载体和传感器丁酶组件之间的相互作用提供第一个结构洞察力.
- 了解抗微生物感应和耐药性的机制.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定Bce模块的结构.
- 生物化学测试用于研究蛋白质-蛋白质相互作用和功能调节.
- 在存在ATP类似物的情况下对复合物的结构分析.
主要成果:
- 确定了一个完整的Bce模块的冷EM结构,揭示了一个意想不到的组装机制.
- 在传感器的histidine kinase组件中观察到显著的结构灵活性.
- 确定了ATP与ABC载体的结合如何激活该复合体.
- 生物化学数据证实了膜蛋白成分之间的功能性交叉调节.
结论:
- Bce模块形成了一个严格调节的酶系统,用于抗微生物抗性.
- 结构洞察力揭示了组装参与细菌防御的膜蛋白复合体的新机制.
- 了解BCE模块为新型抗菌战略提供了潜在的目标.
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