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Crystal structure of AcrB in complex with a single transmembrane subunit reveals another twist

Törnroth-Horsefield, Susanna LU ; Gourdon, Pontus LU ; Horsefield, Rob; Brive, Lars; Yamamoto, Natsuko; Mori, Hirotada; Snijder, Arjan and Neutze, Richard (2007) In Structure with Folding & design 15(12). p.73-1663
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... (More)

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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author
publishing date
type
Contribution to journal
publication status
published
keywords
Escherichia coli Proteins, Models, Molecular, Multidrug Resistance-Associated Proteins, Protein Conformation, Spectroscopy, Fourier Transform Infrared, Tandem Mass Spectrometry, X-Ray Diffraction, Journal Article, Research Support, Non-U.S. Gov't
in
Structure with Folding & design
volume
15
issue
12
pages
73 - 1663
publisher
Cell Press
external identifiers
  • scopus:36749071555
ISSN
0969-2126
DOI
10.1016/j.str.2007.09.023
language
English
LU publication?
no
id
d79ec04c-4e20-4e01-933e-a89937226839
date added to LUP
2017-04-29 15:32:30
date last changed
2017-07-30 05:24:36
@article{d79ec04c-4e20-4e01-933e-a89937226839,
  abstract     = {<p>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.</p>},
  author       = {Törnroth-Horsefield, Susanna and Gourdon, Pontus and Horsefield, Rob and Brive, Lars and Yamamoto, Natsuko and Mori, Hirotada and Snijder, Arjan and Neutze, Richard},
  issn         = {0969-2126},
  keyword      = {Escherichia coli Proteins,Models, Molecular,Multidrug Resistance-Associated Proteins,Protein Conformation,Spectroscopy, Fourier Transform Infrared,Tandem Mass Spectrometry,X-Ray Diffraction,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {12},
  pages        = {73--1663},
  publisher    = {Cell Press},
  series       = {Structure with Folding & design},
  title        = {Crystal structure of AcrB in complex with a single transmembrane subunit reveals another twist},
  url          = {http://dx.doi.org/10.1016/j.str.2007.09.023},
  volume       = {15},
  year         = {2007},
}