多种药物排放的分子基础是由无氧相关的RND输送器
Ryan Lawrence1,2, Mohd Athar3, Muhammad R Uddin4
1School of Biological Sciences, University of Southampton, Southampton, UK.
Nature communications
|December 3, 2025
概括
细菌使用MdtF排泄在恶劣条件下抵抗毒素. 新的冷EM结构揭示了它的机制,显示了在酸性压力下改变的运输和提高效率.
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:
- 细菌拥有抵抗机制,可以在充满挑战的环境中生存,如低氧,极度酸度和营养稀缺等.
- 抗性结节细胞分裂 (RND) 超级家族包括像MdtEF这样的排泄,对于细菌生存至关重要,但具有未知的分子机制.
研究的目的:
- 为了阐明MdtF排水的分子机制,一个由质子动力驱动的传送器.
- 研究MdtF在特定环境压力下对细菌耐药性的作用的结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定大肠杆菌MdtF.的结构.
- 在原生脂质纳米盘中获得结构,包括单点突变和基质结合形式.
主要成果:
- 在MdtF中观察到明显的跨膜状态过渡,增强了质子中继网络.
- 药物结合域和通道中的形态塑性影响基质多特异性.
- 鉴定出了对酸的反应性增加的排泄效率和改变的药物运输全ostery.
结论:
- MdtF表现出独特的跨膜过渡和全调节,有助于其功能.
- 这些发现提供了对细菌异生菌和毒素清除的机制性见解,特别是在酸性压力下的胃肠道中.
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