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PMID:22178925

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Citation

Morrison, EA, DeKoster, GT, Dutta, S, Vafabakhsh, R, Clarkson, MW, Bahl, A, Kern, D, Ha, T and Henzler-Wildman, KA (2012) Antiparallel EmrE exports drugs by exchanging between asymmetric structures. Nature 481:45-50

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.

Links

PubMed PMC3253143 Online version:10.1038/nature10703

Keywords

Antiporters/chemistry; Antiporters/metabolism; Biological Transport; Catalytic Domain; Escherichia coli/chemistry; Escherichia coli/metabolism; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/metabolism; Fluorescence Resonance Energy Transfer; Models, Molecular; Nuclear Magnetic Resonance, Biomolecular; Pharmaceutical Preparations/metabolism; Protein Conformation; Protein Multimerization; Water/chemistry

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

ECOLI:EMRE

GO:0022857: transmembrane transporter activity

ECO:0000314:

F

Figure 1 talks about EmrE'S changes in conformation to allow substrates in.

complete
CACAO 5182

ECOLI:EMRE

enables

GO:0022857: transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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