Interactions of a Bacterial RND Transporter with a Transmembrane Small Protein in a Lipid Environment
Interactions of a Bacterial RND Transporter with a Transmembrane Small Protein in a Lipid Environment
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DOI：
10.1016/j.str.2020.03.013
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发表时间：
2020-06-02
期刊：
影响因子：
5.7
通讯作者：
Luisi, Ben F.
中科院分区：
文献类型：
--
作者：
Du, Dijun;Neuberger, Arthur;Luisi, Ben F.
大肠杆菌中的小蛋白AcrZ与多药外排泵AcrB的跨膜部分相互作用，并增加细菌对该转运蛋白的抗生素底物的子集的耐药性。目前尚不清楚这两种蛋白质的物理结合如何选择性地改变泵对特定底物的活性。在这里，我们报道了AcrB和AcrBZ复合体在脂质环境中的冷冻EM结构，比较表明，由于AcrZ结合，药物结合口袋中发生了构象变化。模拟表明，由于接触表面增加，心磷脂优先与AcrBZ复合体相互作用，我们观察到缺乏AcrZ的细菌在心磷脂缺乏时对氯霉素的敏感性加剧。综上所述，这些数据表明，AcrZ和脂质协同作用，以变构方式调节AcrB的活性。这种由小蛋白质和脂类调节的模式也可能发生在其他膜蛋白上。
The small protein AcrZ in Escherichia coli interacts with the transmembrane portion of the multidrug efflux pump AcrB and increases resistance of the bacterium to a subset of the antibiotic substrates of that transporter. It is not clear how the physical association of the two proteins selectively changes activity of the pump for defined substrates. Here, we report cryo-EM structures of AcrB and the AcrBZ complex in lipid environments, and comparisons suggest that conformational changes occur in the drug-binding pocket as a result of AcrZ binding. Simulations indicate that cardiolipin preferentially interacts with the AcrBZ complex, due to increased contact surface, and we observe that chloramphenicol sensitivity of bacteria lacking AcrZ is exacerbated when combined with cardiolipin deficiency. Taken together, the data suggest that AcrZ and lipid cooperate to allosterically modulate AcrB activity. This mode of regulation by a small protein and lipid may occur for other membrane proteins.