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New free-exchange model of EmrE transport.

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.

SUBMITTER: Robinson AE

PROVIDER: S-EPMC5703289 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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New free-exchange model of EmrE transport.

Robinson Anne E AE Thomas Nathan E NE Morrison Emma A EA Balthazor Bryan M BM Henzler-Wildman Katherine A KA

Proceedings of the National Academy of Sciences of the United States of America 20171107 47

EmrE is a small multidrug resistance transporter found in <i>Escherichia coli</i> 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 substra ...[more]

PMID: 29114048

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Highly coupled transport can be achieved in free-exchange transport models.

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