Conformational flexibility in the multidrug efflux system protein AcrA
Conformational flexibility in the multidrug efflux system protein AcrA
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DOI：
10.1016/j.str.2005.11.015
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发表时间：
2006-03-01
期刊：
影响因子：
5.7
通讯作者：
Ghosh, P
中科院分区：
文献类型：
--
作者：
Mikolosko, J;Bobyk, K;Ghosh, P
在许多革兰氏阴性细菌病原体中，对多种药物的内在耐药性是由耐药诱导细胞分裂外排泵赋予的，所述外排泵由三种基本组分组成，以广泛表征的大肠杆菌AcrA-AcrB-ToIC系统为代表。内膜药物：质子反向转运蛋白AcrB和外膜通道ToIC将化学上不同的化合物输出到细菌细胞外，并且需要第三组分（周质蛋白AcrA）的活性。AcrB和ToIC的晶体结构先前已经确定，我们完成了外排系统的分子图像，通过呈现AcrA的稳定片段的结构。AcrA片段类似于其同源物铜绿假单胞菌MexA的细长镰刀形状，由三个结构域组成：P-桶，硫辛酰基和α-螺旋发夹。值得注意的是，在AcrA的α-螺旋发夹结构域中观察到未被怀疑的构象柔性，这在AcrA构象与ToIC通道开放之间的偶联中具有潜在的机制意义。
Intrinsic resistance to multiple drugs in many gram-negative bacterial pathogens is conferred by resistance nodulation cell division efflux pumps, which are composed of three essential components as typified by the extensively characterized Escherichia coli AcrA-AcrB-ToIC system. The inner membrane drug: proton antiporter AcrB and the outer membrane channel ToIC export chemically diverse compounds out of the bacterial cell, and require the activity of the third component, the periplasmic protein AcrA. The crystal structures of AcrB and ToIC have previously been determined, and we complete the molecular picture of the efflux system by presenting the structure of a stable fragment of AcrA. The AcrA fragment resembles the elongated sickle shape of its homolog Pseudomonas aeruginosa MexA, being composed of three domains: P-barrel, lipoyl, and a-helical hairpin. Notably, unsuspected conformational flexibility in the a-helical hairpin domain of AcrA is observed, which has potential mechanistic significance in coupling between AcrA conformations and ToIC channel opening.