National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM080139
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM072804
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P01GM121203
米国
European Research Council (ERC)
742210
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM143380
米国
引用
ジャーナル: Structure / 年: 2022 タイトル: In situ structure of the AcrAB-TolC efflux pump at subnanometer resolution. 著者: Muyuan Chen / Xiaodong Shi / Zhili Yu / Guizhen Fan / Irina I Serysheva / Matthew L Baker / Ben F Luisi / Steven J Ludtke / Zhao Wang / 要旨: The tripartite AcrAB-TolC assembly, which spans both the inner and outer membranes in Gram-negative bacteria, is an efflux pump that contributes to multidrug resistance. Here, we present the in situ ...The tripartite AcrAB-TolC assembly, which spans both the inner and outer membranes in Gram-negative bacteria, is an efflux pump that contributes to multidrug resistance. Here, we present the in situ structure of full-length Escherichia coli AcrAB-TolC determined at 7 Å resolution by electron cryo-tomography. The TolC channel penetrates the outer membrane bilayer through to the outer leaflet and exhibits two different configurations that differ by a 60° rotation relative to the AcrB position in the pump assembly. AcrA protomers interact directly with the inner membrane and with AcrB via an interface located in proximity to the AcrB ligand-binding pocket. Our structural analysis suggests that these AcrA-bridged interactions underlie an allosteric mechanism for transmitting drug-evoked signals from AcrB to the TolC channel within the pump. Our study demonstrates the power of in situ electron cryo-tomography, which permits critical insights into the function of bacterial efflux pumps.