来自 Staphylococcus aureus 的抗菌流体输送器 QacA 的冷-EM 结构揭示了一个具有全性作用的新型细胞外循环
Puja Majumder1, Shahbaz Ahmed1, Pragya Ahuja1
1Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
The EMBO journal
|July 17, 2023
概括
了解Staphylococcus aureus如何出口抗菌药物可以降低抗菌耐药性. 卡卡运送器的冷EM结构揭示了一个关键的细胞外循环,该循环对于其流出功能至关重要.
科学领域:
- 结构生物学 结构生物学
- 微生物学 微生物学
- 生物化学 生物化学
背景情况:
- 抗菌素耐药性是一个日益增长的全球健康威胁,由诸如药物排放等机制驱动.
- 在金 Staphylococcus 中,QacA 输送体 (主要的促进体超级输送体抗体) 输出阴离子抗菌化合物.
- 了解QacA的结构和功能对于制定打击抗菌素耐药性的策略至关重要.
研究的目的:
- 为了确定QacA传送器的冷电子显微镜 (cryo-EM) 结构.
- 为了研究特定的细胞外循环 (EL7) 在QacA介导的流量活动中的作用.
- 通过QacA阐明抗菌化合物的质子合流出结构的基础.
主要方法:
- 无基质QacA (突变D411N) 与驼类抗体复合的冷EM结构确定.
- 对QacA结构的分析,重点关注向外开放的构造和细胞外螺旋状发针环 (EL7).
- 功能性测试涉及删除或修改EL7循环和与相关传送器 (LfrA,SmvA) 相关的模拟结构.
主要成果:
- 3.6 Å的冷电磁结构显示了QacA的向外开放的形状.
- 在13号和14号跨膜螺旋之间确定了一个细胞外螺旋式发针环 (EL7),并发现它在一些DHA2转运器中得到保护.
- 移除或破坏EL7显著损害了外流活动,而从其他载体中移植EL7恢复了EL7删除的QacA中的功能.
结论:
- 在QacA的抗菌流出机制中,EL7发针环发挥着至关重要的全性作用.
- 对QacA的结构洞察力为理解和潜在地抑制格兰氏阳性病原体中药物流量提供了基础.
- 这些发现凸显了结构元素在DHA2转运器的功能中的重要性.
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