Crystal structure of AcrB in complex with a single transmembrane subunit reveals another twist
Susanna Törnroth-Horsefield1, Pontus Gourdon, Rob Horsefield
1Department of Chemistry, Biochemistry and Biophysics, Gothenburg University, 40530 Gothenburg, Sweden. susanna.tornroth@chem.gu.se
Abstract:
Bacterial drug resistance is a serious concern for human health. Multidrug efflux pumps export a broad variety of substrates out of the cell and thereby convey resistance to the host. In Escherichia coli, the AcrB:AcrA:TolC efflux complex forms a principal transporter for which structures of the individual component proteins have been determined in isolation. Here, we present the X-ray structure of AcrB in complex with a single transmembrane protein, assigned by mass spectrometry as YajC. A specific rotation of the periplasmic porter domain of AcrB is also revealed, consistent with the hypothesized "twist-to-open" mechanism for TolC activation. Growth experiments with yajc-deleted E. coli reveal a modest increase in the organism's susceptibility to beta-lactam antibiotics, but this effect could not conclusively be attributed to the loss of interactions between YajC and AcrB.
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