Journal
STRUCTURE
Volume 28, Issue 6, Pages 625-+Publisher
CELL PRESS
DOI: 10.1016/j.str.2020.03.013
Keywords
-
Funding
- ERC advanced award [742210]
- Wellcome Trust
- GatesCambridge Scholarship
- Herchel Smith Research Studentship
- Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development
- MRC
- BBSRC
- BBSRC [BB/M029573/1] Funding Source: UKRI
- EPSRC [EP/R029407/1] Funding Source: UKRI
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [ZIAHD008855] Funding Source: NIH RePORTER
- European Research Council (ERC) [742210] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
The small protein AcrZ in Escherichia coli interacts with the transmembrane portion of the multidrug efflux pump AcrB and increases resistance of the bacterium to a subset of the antibiotic substrates of that transporter. It is not clear how the physical association of the two proteins selectively changes activity of the pump for defined substrates. Here, we report cryo-EM structures of AcrB and the AcrBZ complex in lipid environments, and comparisons suggest that conformational changes occur in the drug-binding pocket as a result of AcrZ binding. Simulations indicate that cardiolipin preferentially interacts with the AcrBZ complex, due to increased contact surface, and we observe that chloramphenicol sensitivity of bacteria lacking AcrZ is exacerbated when combined with cardiolipin deficiency. Taken together, the data suggest that AcrZ and lipid cooperate to allosterically modulate AcrB activity. This mode of regulation by a small protein and lipid may occur for other membrane proteins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available