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, Katherine A. Henzler-Wildman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalNature
Volume481
Issue number7379
DOIs
StatePublished - Jan 5 2012
Externally publishedYes

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Active Biological Transport
Energy Transfer
Multiple Drug Resistance
Drug Resistance
Cations
Catalytic Domain
Escherichia coli
Membranes
Water
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Morrison, E. A., Dekoster, G. T., Dutta, S., Vafabakhsh, R., Clarkson, M. W., Bahl, A., ... Henzler-Wildman, K. A. (2012). Antiparallel EmrE exports drugs by exchanging between asymmetric structures. Nature, 481(7379), 45-52. https://doi.org/10.1038/nature10703

Antiparallel EmrE exports drugs by exchanging between asymmetric structures. / Morrison, Emma A.; Dekoster, Gregory T.; Dutta, Supratik; Vafabakhsh, Reza; Clarkson, Michael W.; Bahl, Arjun; Kern, Dorothee; Ha, Taekjip; Henzler-Wildman, Katherine A.

In: Nature, Vol. 481, No. 7379, 05.01.2012, p. 45-52.

Research output: Contribution to journalArticle

Morrison, EA, Dekoster, GT, Dutta, S, Vafabakhsh, R, Clarkson, MW, Bahl, A, Kern, D, Ha, T & Henzler-Wildman, KA 2012, 'Antiparallel EmrE exports drugs by exchanging between asymmetric structures', Nature, vol. 481, no. 7379, pp. 45-52. https://doi.org/10.1038/nature10703
Morrison EA, Dekoster GT, Dutta S, Vafabakhsh R, Clarkson MW, Bahl A et al. Antiparallel EmrE exports drugs by exchanging between asymmetric structures. Nature. 2012 Jan 5;481(7379):45-52. https://doi.org/10.1038/nature10703
Morrison, Emma A. ; Dekoster, Gregory T. ; Dutta, Supratik ; Vafabakhsh, Reza ; Clarkson, Michael W. ; Bahl, Arjun ; Kern, Dorothee ; Ha, Taekjip ; Henzler-Wildman, Katherine A. / Antiparallel EmrE exports drugs by exchanging between asymmetric structures. In: Nature. 2012 ; Vol. 481, No. 7379. pp. 45-52.
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