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

TitleAn allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump.
Publication TypeJournal Article
Year of Publication2017
AuthorsWang, Z, Fan, G, Hryc, CF, Blaza, JN, Serysheva, II, Schmid, MF, Chiu, W, Luisi, BF, Du, D
JournalElife
Volume6
Date Published2017 Mar 29
ISSN2050-084X
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.

DOI10.7554/eLife.24905
Alternate JournalElife
Citation Key10.7554/eLife.24905
PubMed ID28355133
PubMed Central IDPMC5404916
Grant ListP41 GM103832 / GM / NIGMS NIH HHS / United States
R01 GM079429 / GM / NIGMS NIH HHS / United States
R01 GM072804 / GM / NIGMS NIH HHS / United States
T15 LM007093 / LM / NLM NIH HHS / United States
S10 OD016279 / OD / NIH HHS / United States