New free-exchange model of EmrE transport. Proc Natl Acad Sci U S A 2017 Nov 21;114(47):E10083-E10091
Date
11/09/2017Pubmed ID
29114048Pubmed Central ID
PMC5703289DOI
10.1073/pnas.1708671114Scopus ID
2-s2.0-85034576395 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
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.
Author List
Robinson AE, Thomas NE, Morrison EA, Balthazor BM, Henzler-Wildman KAAuthor
Emma A. Morrison PhD Assistant Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AntiportersBinding Sites
Biological Transport
Dicyclohexylcarbodiimide
Drug Resistance, Multiple, Bacterial
Escherichia coli
Escherichia coli Proteins
Gene Expression
Hydrogen-Ion Concentration
Kinetics
Molecular Dynamics Simulation
Onium Compounds
Organophosphorus Compounds
Phosphatidylcholines
Phosphatidylglycerols
Protein Binding
Protein Interaction Domains and Motifs
Protein Structure, Secondary
Proteolipids
Protons
Recombinant Proteins
Substrate Specificity
Thermodynamics
Xenobiotics
