Antibiotic Resistance Mediated by the MacB ABC Transporter Family: A Structural and Functional Perspective.

Antibiotic Resistance Mediated by the MacB ABC Transporter Family: A Structural and Functional Perspective.
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DOI:
10.3389/fmicb.2018.00950
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发表时间:
2018
影响因子:
5.2
通讯作者:
Koronakis V
Koronakis V
中科院分区:
生物学2区
文献类型:
--
作者:
Greene NP;Kaplan E;Crow A;Koronakis V

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MacB ABC转运蛋白与MacA接头蛋白和TolC外膜出口管形成一个三方外排泵,从革兰氏阴性菌中排出抗生素和输出毒力因子。在这里,我们回顾了最近关于MacB及其同源物的结构和功能数据。MacB具有与其他ABC转运蛋白不同的折叠结构,并使用一种称为机械传递的独特分子机制。与其他细菌ABC转运蛋白不同,MacB不转运底物穿过其所基于的内膜,而是将细胞质ATP水解与跨膜构象变化结合在一起,用于在细胞质外空间进行工作。在MacAB-TolC三方泵中,机械传递驱动抗生素外排,并通过TolC出口管道从质周空间输出蛋白质毒素。来自致病菌的同源三方系统类似地输出蛋白样信号分子、毒力因子和铁载体。此外,许多macb样ABC转运蛋白不形成三方泵,而是在多种细胞过程中起作用,包括抗生素感应、细胞分裂和脂蛋白运输。
The MacB ABC transporter forms a tripartite efflux pump with the MacA adaptor protein and TolC outer membrane exit duct to expel antibiotics and export virulence factors from Gram-negative bacteria. Here, we review recent structural and functional data on MacB and its homologs. MacB has a fold that is distinct from other structurally characterized ABC transporters and uses a unique molecular mechanism termed mechanotransmission. Unlike other bacterial ABC transporters, MacB does not transport substrates across the inner membrane in which it is based, but instead couples cytoplasmic ATP hydrolysis with transmembrane conformational changes that are used to perform work in the extra-cytoplasmic space. In the MacAB-TolC tripartite pump, mechanotransmission drives efflux of antibiotics and export of a protein toxin from the periplasmic space via the TolC exit duct. Homologous tripartite systems from pathogenic bacteria similarly export protein-like signaling molecules, virulence factors and siderophores. In addition, many MacB-like ABC transporters do not form tripartite pumps, but instead operate in diverse cellular processes including antibiotic sensing, cell division and lipoprotein trafficking.
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