组装和抑制可转移的TMexCD1-TOprJ1排水
Yu Shi1,2, Mengyuan Li1,2,3, Tao Cui4
1Department of General Intensive Care Unit of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Nature communications
|November 14, 2025
概括
由TMexCD1-TOprJ1排泄介导的tigecycline耐药性是一个日益增长的威胁. 低温电磁结构揭示了的结构.
科学领域:
- 结构生物学 结构生物学
- 微生物学 微生物学
- 药物耐药性 药物耐药性 药物耐药性
背景情况:
- 血传播的tmexCD1-toprJ1赋予了tigecycline耐药性,影响了最后的抗生素疗效.
- 了解这种排泄的分子机制对于对抗细菌感染至关重要.
研究的目的:
- 为了确定TMexCD1-TOprJ1排泄的冷电子显微镜 (cryo-EM) 结构.
- 阐明TMexCD1-TOprJ1组合和由NMP抑制的分子基础.
主要方法:
- 确定了TMexCD1-TOprJ1的两个冷EM结构,分辨率为2.97 Å和3.0 Å.
- 分析了三方架构,原体体积测量 (3:6:3),以及组件间的相互作用.
主要成果:
- 揭示了一种3:6:3质子体立体测量 (TOprJ1:TMexC1:TMexD1) 形成一个长长的,棒状的.
- 确定了TMexC1作为一个连接TOprJ1和TMexD1引擎的周等离子适配器的作用.
- 标志着TMexD1三元体的独特静止状态和基质/抑制剂加载腔.
结论:
- 提供了关于可转移TMexCD1-TOprJ1排泄的组装和抑制的分子见解.
- 这些发现支持开发针对这种必不可少的耐药机制的新型抗微生物药物.
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