...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Kinetic control of TolC recruitment by multidrug efflux complexes
【24h】

Kinetic control of TolC recruitment by multidrug efflux complexes

机译：多药外排复合物对TolC募集的动力学控制

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In Gram-negative pathogens, multidrug efflux pumps that provide clinically significant levels of antibiotic resistance function as three-component complexes. They are composed of the inner membrane transporters belonging to one of three superfamilies of proteins, RND, ABC, or MF; periplasmic proteins belonging to the membrane fusion protein (MFP) family; and outer membrane channels exemplified by the Escherichia coli TolC. The three-component complexes span the entire two-membrane envelope of Gram-negative bacteria and expel toxic molecules from the cytoplasmic membrane to the medium. The architecture of these complexes is expected to vary significantly because of the structural diversity of the inner membrane transporters. How the three-component pumps are assembled, their architecture, and their dynamics remain unclear. In this study, we reconstituted interactions and compared binding kinetics of the E. coli TolC with AcrA, MacA, and EmrA, the periplasmic MFPs that function in multidrug efflux with transporters from the RND, ABC, and MF superfamilies, respectively. By using surface plasmon resonance, we demonstrate that TolC interactions with MFPs are highly dynamic and sensitive to pH. The affinity of TolC to MFPs decreases in the order MacA > EmrA > AcrA. We further show that MFPs are prone to oligomerization, but differ dramatically from each other in oligomerization kinetics and stability of oligomers. The propensity of MFPs to oligomerize correlates with the stability of MFP-TolC complexes and structural features of inner membrane transporters. We propose that recruitment of TolC by various MFPs is determined not only by kinetics of MFP-TolC interactions but also by oligomerization kinetics of MFPs and pH.
机译：在革兰氏阴性病原体中，提供临床上显着水平的抗生素抗性的多药外排泵可作为三组分复合物发挥作用。它们是由属于RND，ABC或MF三种蛋白质超家族之一的内膜转运蛋白组成的。属于膜融合蛋白（MFP）家族的周质蛋白；和外膜通道以大肠杆菌TolC为例。这三种成分的复合物跨越了革兰氏阴性细菌的整个两膜包膜，并将有毒分子从细胞质膜排到培养基中。由于内膜转运蛋白的结构多样性，预计这些复合物的结构会发生很大变化。三组分泵的组装方式，结构和动力仍不清楚。在这项研究中，我们重构了相互作用，并比较了大肠杆菌TolC与AcrA，MacA和EmrA的结合动力学，AcrA，MacA和EmrA分别与RND，ABC和MF超家族的转运蛋白在多药外排中起作用的周质MFP。通过使用表面等离子体激元共振，我们证明与MFP的TolC相互作用是高度动态的，并且对pH敏感。 TolC对MFP的亲和力以MacA> EmrA> AcrA的顺序降低。我们进一步表明，MFPs易于低聚，但在低聚动力学和低聚物稳定性方面存在很大差异。 MFP的低聚倾向与MFP-TolC复合物的稳定性和内膜转运蛋白的结构特征相关。我们建议，由各种MFP募集的TolC不仅取决于MFP-TolC相互作用的动力学，还取决于MFP和pH的低聚动力学。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号