The AcrAB–TolC efflux pump is widespread in Gram-negative bacteria and confers resistance to multiple antibiotics, as it can extrude a large repertoire of chemically diverse compounds. Du et al. now present the first three-dimensional crystal structure of the entire pump from Escherichia coli, in complex with its partner protein AcrZ. The pump consists of an AcrB trimer in the inner membrane and a TolC trimer in the outer membrane, which are linked by a periplasmic AcrA hexamer. The authors observed a continuous channel that extends from AcrB through AcrA and into TolC, which is probably the exit conduit for substrates. As TolC is closed in the resting state, the authors propose that it adopts an open conformation owing to direct interactions with AcrA and allosteric cooperativity within TolC. The structure also suggests that the modulatory effects of AcrZ on substrate preference are probably mediated by allosteric interactions with AcrB.
References
Du, D. et al. Structure of the AcrAB–TolC multidrug efflux pump. Nature http://dx.doi.org/10.1038/nature13205 (2014)
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Kåhrström, C. First model of the entire AcrAB–TolC efflux pump. Nat Rev Microbiol 12, 395 (2014). https://doi.org/10.1038/nrmicro3277
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DOI: https://doi.org/10.1038/nrmicro3277