An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump

Zhao Wang; Guizhen Fan; Corey F Hryc; James N Blaza; Irina I Serysheva; Michael F Schmid; Wah Chiu; Ben F Luisi; Dijun Du

doi:10.7554/eLife.24905

An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump

Zhao Wang, Guizhen Fan, Corey F Hryc, James N Blaza, Irina I Serysheva, Michael F Schmid, Wah Chiu, Ben F Luisi, Dijun Du

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

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 Escherichia coli 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.

Original language	English
Article number	e24905
Number of pages	19
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.24905
Publication status	Published - 29 Mar 2017

Bibliographical note

Keywords

Allosteric Regulation
Anti-Bacterial Agents/metabolism
Carrier Proteins/chemistry
Cryoelectron Microscopy
Escherichia coli/chemistry
Escherichia coli Proteins/chemistry
Protein Conformation

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10.7554/eLife.24905Licence: CC BY

elife-24905-v2
© 2017, Wang et al.
Final published version, 2.92 MBLicence: CC BY

https://www.repository.cam.ac.uk/handle/1810/264550Licence: CC BY

Jamie Blaza
- jamie.blazayork.acuk
- Chemistry - Senior Lecturer
Person: Academic

Cite this

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title = "An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump",

abstract = "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 Escherichia coli 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.",

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T1 - An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump

AU - Wang, Zhao

AU - Fan, Guizhen

AU - Hryc, Corey F

AU - Blaza, James N

AU - Serysheva, Irina I

AU - Schmid, Michael F

AU - Chiu, Wah

AU - Luisi, Ben F

AU - Du, Dijun

PY - 2017/3/29

Y1 - 2017/3/29

N2 - 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 Escherichia coli 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.

AB - 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 Escherichia coli 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.

KW - Allosteric Regulation

KW - Anti-Bacterial Agents/metabolism

KW - Carrier Proteins/chemistry

KW - Cryoelectron Microscopy

KW - Escherichia coli/chemistry

KW - Escherichia coli Proteins/chemistry

KW - Protein Conformation

U2 - 10.7554/eLife.24905

DO - 10.7554/eLife.24905

M3 - Article

C2 - 28355133

SN - 2050-084X

VL - 6

JO - eLife

JF - eLife

M1 - e24905

ER -

An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump

Abstract

Bibliographical note

Keywords

Access to Document

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Jamie Blaza

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