Crystal structure of AcrB in complex with a single transmembrane subunit reveals another twist
(2007) In Structure 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.
(Less)
- author
- Törnroth-Horsefield, Susanna LU ; Gourdon, Pontus LU ; Horsefield, Rob ; Brive, Lars ; Yamamoto, Natsuko ; Mori, Hirotada ; Snijder, Arjan and Neutze, Richard
- publishing date
- 2007-12
- 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
- volume
- 15
- issue
- 12
- pages
- 73 - 1663
- publisher
- Cell Press
- external identifiers
-
- scopus:36749071555
- pmid:18073115
- 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
- 2024-04-14 09:34:01
@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}}, 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}}, language = {{eng}}, number = {{12}}, pages = {{73--1663}}, publisher = {{Cell Press}}, series = {{Structure}}, 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}}, doi = {{10.1016/j.str.2007.09.023}}, volume = {{15}}, year = {{2007}}, }