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Structure paper

TitleAn allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump.
Journal, issue, pagesElife, Vol. 6, Year 2017
Publish dateMar 29, 2017
AuthorsZhao Wang / Guizhen Fan / Corey F Hryc / James N Blaza / Irina I Serysheva / Michael F Schmid / Wah Chiu / Ben F Luisi / Dijun Du /
PubMed AbstractBacterial efflux pumps confer multidrug resistance by transporting diverse antibiotics from the cell. In Gram-negative bacteria, some of these pumps form multi-protein assemblies that span the cell ...Bacterial efflux pumps confer multidrug resistance by transporting diverse antibiotics from the cell. In Gram-negative bacteria, some of these pumps form multi-protein assemblies that span the cell envelope. Here, we report the near-atomic resolution cryoEM structures of the AcrAB-TolC multidrug efflux pump in resting and drug transport states, revealing a quaternary structural switch that allosterically couples and synchronizes initial ligand binding with channel opening. Within the transport-activated state, the channel remains open even though the pump cycles through three distinct conformations. Collectively, our data provide a dynamic mechanism for the assembly and operation of the AcrAB-TolC pump.
External linksElife / PubMed:28355133 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.2 - 6.5 Å
Structure data

EMDB-3636, PDB-5ng5:
multi-drug efflux; membrane transport; RND superfamily; Drug resistance
Method: EM (single particle) / Resolution: 6.5 Å

EMDB-8636, PDB-5v5s:
multi-drug efflux; membrane transport; RND superfamily; Drug resistance
Method: EM (single particle) / Resolution: 6.5 Å

EMDB-8640: Asymmetric structure of AcrAB-TolC tripartite multi drug efflux pump
PDB-5o66: Asymmetric AcrABZ-TolC
Method: EM (single particle) / Resolution: 5.9 Å

PDB-5nc5:
Crystal structure of AcrBZ in complex with antibiotic puromycin
Method: X-RAY DIFFRACTION / Resolution: 3.2 Å

Chemicals

ChemComp-LMT:
DODECYL-BETA-D-MALTOSIDE / detergent*YM

ChemComp-D12:
DODECANE / Dodecane

ChemComp-D10:
DECANE / Decane

ChemComp-DD9:
nonane / Nonane

ChemComp-PUY:
PUROMYCIN / antibiotic, inhibitor*YM / Puromycin

ChemComp-HEX:
HEXANE / Hexane

ChemComp-HOH:
WATER / Water

ChemComp-5QF:
6-[2-(3,4-dimethoxyphenyl)ethylsulfanyl]-8-[4-(2-methoxyethyl)piperazin-1-yl]-3,3-dimethyl-1,4-dihydropyrano[3,4-c]pyridine-5-carbonitrile

Source
  • escherichia coli (E. coli)
  • Escherichia coli
  • escherichia coli k12 (bacteria)
  • Escherichia coli (strain K12) (bacteria)
  • escherichia coli k-12 (bacteria)
  • escherichia coli o157:h7 (bacteria)
KeywordsTRANSPORT PROTEIN / Membrane transporter / Multidrug efflux pump / MEMBRANE PROTEIN / multi-drug efflux; membrane transport; RND superfamily; Drug resistance / multi-drug efflux / membrane transport / RND superfamily / Drug resistance

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