Greene Nicholas P, Kaplan Elise, Crow Allister, Koronakis Vassilis
Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
School of Life Sciences, University of Warwick, Coventry, United Kingdom.
Front Microbiol. 2018 May 28;9:950. doi: 10.3389/fmicb.2018.00950. eCollection 2018.
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.
MacB ABC转运蛋白与MacA衔接蛋白和TolC外膜输出通道形成一个三方外排泵，以排出抗生素并从革兰氏阴性细菌中输出毒力因子。在此，我们综述了关于MacB及其同源物的最新结构和功能数据。MacB具有与其他已解析结构的ABC转运蛋白不同的折叠方式，并采用一种称为机械传导的独特分子机制。与其他细菌ABC转运蛋白不同，MacB并不在其所在的内膜上跨膜转运底物，而是将细胞质ATP水解与跨膜构象变化偶联起来，这些构象变化用于在胞外空间做功。在MacAB-TolC三方泵中，机械传导驱动抗生素从周质空间经TolC输出通道排出以及一种蛋白质毒素的输出。来自致病细菌的同源三方系统同样输出类似蛋白质的信号分子、毒力因子和铁载体。此外，许多类MacB ABC转运蛋白并不形成三方泵，而是在包括抗生素感应、细胞分裂和脂蛋白运输等多种细胞过程中发挥作用。
