Publication Date:
2011-12-20
Description:
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. Forster 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253143/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253143/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morrison, Emma A -- DeKoster, Gregory T -- Dutta, Supratik -- Vafabakhsh, Reza -- Clarkson, Michael W -- Bahl, Arjun -- Kern, Dorothee -- Ha, Taekjip -- Henzler-Wildman, Katherine A -- 1R01GM095839/GM/NIGMS NIH HHS/ -- R01 GM095839/GM/NIGMS NIH HHS/ -- R01 GM095839-01A1/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Dec 18;481(7379):45-50. doi: 10.1038/nature10703.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22178925" target="_blank"〉PubMed〈/a〉
Keywords:
Antiporters/*chemistry/*metabolism
;
Biological Transport
;
Catalytic Domain
;
Escherichia coli/*chemistry/metabolism
;
Escherichia coli Proteins/*chemistry/*metabolism
;
Fluorescence Resonance Energy Transfer
;
Models, Molecular
;
Nuclear Magnetic Resonance, Biomolecular
;
Pharmaceutical Preparations/*metabolism
;
Protein Conformation
;
Protein Multimerization
;
Water/chemistry
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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