Wang Zhao, Fan Guizhen, Hryc Corey F, Blaza James N, Serysheva Irina I, Schmid Michael F, Chiu Wah, Luisi Ben F, Du Dijun
National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, United States.
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States.
Elife. 2017 Mar 29;6:e24905. doi: 10.7554/eLife.24905.
Bacterial efflux pumps confer multidrug resistance by transporting diverse antibiotics from the cell. In Gram-negative bacteria, some of these pumps form multi-protein assemblies that span the cell envelope. Here, we report the near-atomic resolution cryoEM structures of the AcrAB-TolC multidrug efflux pump in resting and drug transport states, revealing a quaternary structural switch that allosterically couples and synchronizes initial ligand binding with channel opening. Within the transport-activated state, the channel remains open even though the pump cycles through three distinct conformations. Collectively, our data provide a dynamic mechanism for the assembly and operation of the AcrAB-TolC pump.
细菌外排泵通过将多种抗生素从细胞内转运出去而赋予多药耐药性。在革兰氏阴性菌中，其中一些泵形成跨越细胞包膜的多蛋白组装体。在此，我们报告了处于静息状态和药物转运状态的AcrAB-TolC多药外排泵的近原子分辨率冷冻电镜结构，揭示了一种四级结构转换，该转换通过变构作用将初始配体结合与通道开放耦合并同步。在转运激活状态下，即使泵经历三种不同的构象循环，通道仍保持开放。总体而言，我们的数据为AcrAB-TolC泵的组装和运作提供了一种动态机制。
