An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump
eLife Sciences Publications
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Wang, Z., Fan, G., Hryc, C., Blaza, J., Serysheva, I., Schmid, M., Chiu, W., et al. (2017). An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump. eLife, 6 (e24905)https://doi.org/10.7554/eLife.24905
Bacterial efflux pumps confer multidrug resistance by transporting diverse antibiotics from the cell. In Gram-negative bacteria, some of these pumps form multi-protein assemblies that span the cell envelope. Here, we report the near-atomic resolution cryoEM structures of the Escherichia coli AcrAB-TolC multidrug efflux pump in resting and drug transport states, revealing a quaternary structural switch that allosterically couples and synchronizes initial ligand binding with channel opening. Within the transport-activated state, the channel remains open even though the pump cycles through three distinct conformations. Collectively, our data provide a dynamic mechanism for the assembly and operation of the AcrAB-TolC pump.
biophysics, structural biology, AcrA, AcrZ, carb, drug efflux, E. coli, TolC, tripartite assembly
This work was supported by the American Heart Association (16RNT29720001), and Grants from National Institutes of Health (P41GM103832, R01GM079429, R01GM072804, S10OD016279), the Wellcome trust, the Human Frontiers Science Program and MRC Mitochondrial Biology Unit (Grant number: U105663141). CFH is supported by a pre-doctoral training fellowship from the Keck Center of the Gulf Coast Consortia, on the NLM Training Program in Biomedical Informatics (Grant No. T15LM007093). We acknowledge the computing resources provided by the Center for Computational and Integrative Biomedical Research of Baylor College of Medicine and the Texas Advanced Computing Center at the University of Texas at Austin funded by the National Science Foundation (NSF) through grant ACI-1134872.
MRC (MC_PC_14116 v2)
External DOI: https://doi.org/10.7554/eLife.24905
This record's URL: https://www.repository.cam.ac.uk/handle/1810/264550