Crystal structure of AcrB in complex with a single transmembrane subunit reveals another twist.
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.
Törnroth-Horsefield
Susanna
S
Department of Chemistry, Biochemistry and Biophysics, Gothenburg University, 40530 Gothenburg, Sweden. susanna.tornroth@chem.gu.se
Gourdon
Pontus
P
Horsefield
Rob
R
Brive
Lars
L
Yamamoto
Natsuko
N
Mori
Hirotada
H
Snijder
Arjan
A
Neutze
Richard
R
D029968:Escherichia coli Proteins / Q000737:chemistry*; D008958:Models, Molecular; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared; D053719:Tandem Mass Spectrometry; D014961:X-Ray Diffraction
D029968:Escherichia coli Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C083496:AcrB protein, E coli