Protonation of a glutamate residue modulates the dynamics of the drug transporter EmrE

Anindita Gayen, Maureen Leninger, Nathaniel Traaseth

Research output: Contribution to journalArticle

Abstract

Secondary active transport proteins play a central role in conferring bacterial multidrug resistance. In this work, we investigated the proton-coupled transport mechanism for the Escherichia coli drug efflux pump EmrE using NMR spectroscopy. Our results show that the global conformational motions necessary for transport are modulated in an allosteric fashion by the protonation state of a membrane-embedded glutamate residue. These observations directly correlate with the resistance phenotype for wild-type EmrE and the E14D mutant as a function of pH. Furthermore, our results support a model in which the pH gradient across the inner membrane of E. coli may be used on a mechanistic level to shift the equilibrium of the transporter in favor of an inward-open resting conformation poised for drug binding.

Original languageEnglish (US)
Pages (from-to)141-145
Number of pages5
JournalNature Chemical Biology
Volume12
Issue number3
DOIs
StatePublished - Feb 1 2016

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Glutamic Acid
Escherichia coli
Proton-Motive Force
Membranes
Active Biological Transport
Multiple Drug Resistance
Pharmaceutical Preparations
Protons
Carrier Proteins
Magnetic Resonance Spectroscopy
Phenotype

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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Protonation of a glutamate residue modulates the dynamics of the drug transporter EmrE. / Gayen, Anindita; Leninger, Maureen; Traaseth, Nathaniel.

In: Nature Chemical Biology, Vol. 12, No. 3, 01.02.2016, p. 141-145.

Research output: Contribution to journalArticle

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