Antiparallel EmrE exports drugs by exchanging between asymmetric structures

Emma A. Morrison, Gregory T. DeKoster, Supratik Dutta, Reza Vafabakhsh, Michael W. Clarkson, Arjun Bahl, Dorothee Kern, Taekjip Ha and Katherine A. Henzler-Wildman ()
Additional contact information
Emma A. Morrison: Washington University School of Medicine
Gregory T. DeKoster: Washington University School of Medicine
Supratik Dutta: Washington University School of Medicine
Reza Vafabakhsh: University of Illinois at Urbana-Champaign
Michael W. Clarkson: Brandeis University
Arjun Bahl: Washington University School of Medicine
Dorothee Kern: Brandeis University
Taekjip Ha: University of Illinois at Urbana-Champaign
Katherine A. Henzler-Wildman: Washington University School of Medicine

Nature, 2012, vol. 481, issue 7379, 45-50

Abstract: Abstract 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.

Date: 2012
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature10703 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:481:y:2012:i:7379:d:10.1038_nature10703

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature10703

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().