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TitleInteractions of a Bacterial RND Transporter with a Transmembrane Small Protein in a Lipid Environment.
Journal, issue, pagesStructure, Vol. 28, Issue 6, Page 625-634.e6, Year 2020
Publish dateJun 2, 2020
AuthorsDijun Du / Arthur Neuberger / Mona Wu Orr / Catherine E Newman / Pin-Chia Hsu / Firdaus Samsudin / Andrzej Szewczak-Harris / Leana M Ramos / Mekdes Debela / Syma Khalid / Gisela Storz / Ben F Luisi /
PubMed AbstractThe 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 ...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.
External linksStructure / PubMed:32348749 / PubMed Central
MethodsEM (single particle)
Resolution3.17 - 3.46 Å
Structure data

EMDB-10182, PDB-6sgr:
Cryo-EM structure of Escherichia coli AcrBZ and DARPin in Saposin A-nanodisc with cardiolipin
Method: EM (single particle) / Resolution: 3.17 Å

EMDB-10183, PDB-6sgs:
Cryo-EM structure of Escherichia coli AcrBZ and DARPin in Saposin A-nanodisc
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-10184, PDB-6sgt:
Cryo-EM structure of Escherichia coli AcrB and DARPin in Saposin A-nanodisc with cardiolipin
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-10185, PDB-6sgu:
Cryo-EM structure of Escherichia coli AcrB and DARPin in Saposin A-nanodisc
Method: EM (single particle) / Resolution: 3.27 Å

Source
  • escherichia coli k-12 (bacteria)
  • synthetic construct (others)
  • shigella boydii 965-58 (bacteria)
  • escherichia coli k12 (bacteria)
KeywordsMEMBRANE PROTEIN / RND transporter / efflux pump / drug transport / antibiotic resistance / lipid nanodisc

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