Protonation-dependent conformational dynamics of the multidrug transporter EmrE

Proceedings of the National Academy of Sciences of the United States of America
Reza DastvanHassane S McHaourab

Abstract

The small multidrug transporter from Escherichia coli, EmrE, couples the energetically uphill extrusion of hydrophobic cations out of the cell to the transport of two protons down their electrochemical gradient. Although principal mechanistic elements of proton/substrate antiport have been described, the structural record is limited to the conformation of the substrate-bound state, which has been shown to undergo isoenergetic alternating access. A central but missing link in the structure/mechanism relationship is a description of the proton-bound state, which is an obligatory intermediate in the transport cycle. Here we report a systematic spin labeling and double electron electron resonance (DEER) study that uncovers the conformational changes of EmrE subsequent to protonation of critical acidic residues in the context of a global description of ligand-induced structural rearrangements. We find that protonation of E14 leads to extensive rotation and tilt of transmembrane helices 1-3 in conjunction with repacking of loops, conformational changes that alter the coordination of the bound substrate and modulate its access to the binding site from the lipid bilayer. The transport model that emerges from our data posits a proton-bo...Continue Reading

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Citations

Feb 9, 2017·Chemical Reviews·Ilia G Denisov, Stephen G Sligar
Jun 12, 2018·ELife·Erika A RiedererFrancis I Valiyaveetil
Oct 6, 2018·The Journal of Biological Chemistry·Nathan E ThomasKatherine A Henzler-Wildman
Jan 13, 2019·Applied and Environmental Microbiology·Gavin KurganXuan Wang
Nov 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·Anne E RobinsonKatherine A Henzler-Wildman
Jul 22, 2018·Proceedings of the National Academy of Sciences of the United States of America·Josh V VermaasEmad Tajkhorshid
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Aug 1, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jana Shen
Nov 29, 2020·Nature Communications·Ali A KermaniRandy B Stockbridge
Jan 10, 2021·Nature Communications·Alexander A ShcherbakovMei Hong
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Mar 29, 2021·Journal of Molecular Biology·Derek P ClaxtonHassane S Mchaourab
Apr 11, 2021·The Journal of Biological Chemistry·Steven CastellanoJosé D Faraldo-Gómez
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Oct 7, 2021·PLoS Computational Biology·Jakub JuraszMiłosz Wieczór

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