Transport of lipophilic carboxylates is mediated by transmembrane helix 2 in multidrug transporter AcrB.
Transport of lipophilic carboxylates is mediated by transmembrane helix 2 in multidrug transporter AcrB.
复制标题
DOI：
10.1038/ncomms13819
复制
发表时间：
2016-12-16
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
多药外排泵的部署是革兰氏阴性细菌细胞暴露于抗菌剂时的强大防御机制。大肠杆菌中主要的多药外排转运系统AcrAB-TolC是一个以质子动力为能量来源的三方系统。多特异性底物结合模块AcrB使用各种途径从内膜的周质和外小叶隔离药物。在这里，我们报告的不对称AcrB结构在复杂的夫西地酸在2.5 μ m的分辨率和突变分析推定的夫西地酸结合位点的跨膜结构域。由跨膜螺旋1（TM 1）和TM 2之间的界面形成的凹槽特异性结合夫西地酸和其他亲脂性羧化药物。我们建议，这些绑定的药物被积极位移的向上运动TM 2对AcrB周质转运域响应质子化事件在跨膜结构域。 AcrAB-TolC多药外排泵的AcrB模块将药物从内膜的周质和外小叶隔离。在这里，Oswald等人提供了亲脂性羧化底物结合到跨膜螺旋TM 1和TM 2之间的沟的证据，用于通过TM 2的向上移动进一步转运。
The deployment of multidrug efflux pumps is a powerful defence mechanism for Gram-negative bacterial cells when exposed to antimicrobial agents. The major multidrug efflux transport system in Escherichia coli, AcrAB–TolC, is a tripartite system using the proton-motive force as an energy source. The polyspecific substrate-binding module AcrB uses various pathways to sequester drugs from the periplasm and outer leaflet of the inner membrane. Here we report the asymmetric AcrB structure in complex with fusidic acid at a resolution of 2.5 Å and mutational analysis of the putative fusidic acid binding site at the transmembrane domain. A groove shaped by the interface between transmembrane helix 1 (TM1) and TM2 specifically binds fusidic acid and other lipophilic carboxylated drugs. We propose that these bound drugs are actively displaced by an upward movement of TM2 towards the AcrB periplasmic porter domain in response to protonation events in the transmembrane domain. The AcrB module of the AcrAB-TolC multidrug efflux pump sequesters drugs from the periplasm and outer leaflet of the inner membrane. Here, Oswald et al. provide evidence that lipophilic carboxylated substrates bind to a groove between transmembrane helices TM1 and TM2, for further transport by an upward movement of TM2.
登录
查看更多内容
影响因子：
4.8
作者：
Eda, S;Maseda, H;Nakae, T
通讯作者：
Nakae, T
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Chen VB;Arendall WB 3rd;Headd JJ;Keedy DA;Immormino RM;Kapral GJ;Murray LW;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
7.7
作者：
Eicher, Thomas;Seeger, Markus A.;Pos, Klaas M.
通讯作者：
Pos, Klaas M.
影响因子：
3.2
作者：
Guan, L;Nakae, T
通讯作者：
Nakae, T