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Proc Natl Acad Sci U S A. 2017 Nov 21;114(47):E10083-E10091. doi: 10.1073/pnas.1708671114. Epub 2017 Nov 7.

New free-exchange model of EmrE transport.

Author information

1
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
2
Department of Biochemistry, University of Wisconsin at Madison, Madison, WI 53706.
3
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110; henzlerwildm@wisc.edu.

Abstract

EmrE is a small multidrug resistance transporter found in Escherichia coli that confers resistance to toxic polyaromatic cations due to its proton-coupled antiport of these substrates. Here we show that EmrE breaks the rules generally deemed essential for coupled antiport. NMR spectra reveal that EmrE can simultaneously bind and cotransport proton and drug. The functional consequence of this finding is an exceptionally promiscuous transporter: not only can EmrE export diverse drug substrates, it can couple antiport of a drug to either one or two protons, performing both electrogenic and electroneutral transport of a single substrate. We present a free-exchange model for EmrE antiport that is consistent with these results and recapitulates ∆pH-driven concentrative drug uptake. Kinetic modeling suggests that free exchange by EmrE sacrifices coupling efficiency but boosts initial transport speed and drug release rate, which may facilitate efficient multidrug efflux.

KEYWORDS:

NMR; coupled transport; membrane protein; multidrug transport; protein dynamics

PMID:
29114048
PMCID:
PMC5703289
DOI:
10.1073/pnas.1708671114
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflict of interest.

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