Antiparallel EmrE exports drugs by exchanging between asymmetric structures. Nature 2011 Dec 18;481(7379):45-50
Date
12/20/2011Pubmed ID
22178925Pubmed Central ID
PMC3253143DOI
10.1038/nature10703Scopus ID
2-s2.0-84855455990 (requires institutional sign-in at Scopus site) 163 CitationsAbstract
Small multidrug resistance transporters provide an ideal system to study the minimal requirements for active transport. EmrE is one such transporter in Escherichia coli. It exports a broad class of polyaromatic cation substrates, thus conferring resistance to drug compounds matching this chemical description. However, a great deal of controversy has surrounded the topology of the EmrE homodimer. Here we show that asymmetric antiparallel EmrE exchanges between inward- and outward-facing states that are identical except that they have opposite orientation in the membrane. We quantitatively measure the global conformational exchange between these two states for substrate-bound EmrE in bicelles using solution NMR dynamics experiments. Förster resonance energy transfer reveals that the monomers within each dimer are antiparallel, and paramagnetic relaxation enhancement NMR experiments demonstrate differential water accessibility of the two monomers within each dimer. Our experiments reveal a 'dynamic symmetry' that reconciles the asymmetric EmrE structure with the functional symmetry of residues in the active site.
Author List
Morrison EA, DeKoster GT, Dutta S, Vafabakhsh R, Clarkson MW, Bahl A, Kern D, Ha T, 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
AntiportersBiological Transport
Catalytic Domain
Escherichia coli
Escherichia coli Proteins
Fluorescence Resonance Energy Transfer
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Pharmaceutical Preparations
Protein Conformation
Protein Multimerization
Water
