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Antiparallel EmrE exports drugs by exchanging between asymmetric structures
Emma A Morrison1, Gregory T DeKoster, Supratik Dutta
1Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Nature
|December 20, 2011
Summary
Escherichia coli EmrE transporters, crucial for drug resistance, were studied. We found asymmetric antiparallel EmrE monomers dynamically exchange between inward- and outward-facing states, explaining functional symmetry.
Area of Science:
- Biochemistry
- Structural Biology
- Membrane Transport
Background:
- Small multidrug resistance (SMR) transporters are key to understanding active transport mechanisms.
- EmrE from Escherichia coli exports polyaromatic cation substrates, conferring multidrug resistance.
- The homodimer topology of EmrE has been a subject of significant scientific debate.
Purpose of the Study:
- To elucidate the conformational dynamics and membrane topology of the EmrE transporter.
- To reconcile the structural asymmetry of EmrE with the functional symmetry observed in its active site.
Main Methods:
- Solution Nuclear Magnetic Resonance (NMR) dynamics experiments in bicelles.
- Förster Resonance Energy Transfer (FRET) to determine monomer orientation.
- Paramagnetic Relaxation Enhancement (PRE) NMR to assess water accessibility.
Main Results:
- Demonstrated that asymmetric antiparallel EmrE monomers exchange between inward- and outward-facing conformations.
- Quantitatively measured the global conformational exchange dynamics of substrate-bound EmrE.
- Revealed differential water accessibility of monomers within the EmrE dimer, indicating asymmetry.
Conclusions:
- EmrE exhibits 'dynamic symmetry,' where asymmetric monomers achieve functional symmetry through conformational exchange.
- This dynamic mechanism explains how EmrE maintains transport activity despite structural asymmetry.
- Provides a novel perspective on the minimal requirements for active transport in membrane proteins.
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