title: An emerging consensus for the structure of EmrE.
abstract: The archetypical member of the small multidrug-resistance family is EmrE, a multidrug transporter that extrudes toxic polyaromatic cations from the cell coupled to the inward movement of protons down a concentration gradient. The architecture of EmrE was first defined from the analysis of two-dimensional crystals by cryoelectron microscopy (cryo-EM), which showed that EmrE was an unusual asymmetric dimer formed from a bundle of eight alpha-helices. The most favoured interpretation of the structure was that the monomers were oriented in opposite orientations in the membrane in an antiparallel orientation. A model was subsequently built based upon the cryo-EM data and evolutionary constraints and this model was consistent with mutagenic data indicating which amino-acid residues were important for substrate binding and transport. Two X-ray structures that differed significantly from the cryo-EM structure were subsequently retracted owing to a data-analysis error. However, the revised X-ray structure with substrate bound is extremely similar to the model built from the cryo-EM structure (r.m.s.d. of 1.4 A), suggesting that the proposed antiparallel orientation of the monomers is indeed correct; this represents a new structural paradigm in membrane-protein structures. The vast majority of mutagenic and biochemical data corroborate this structure, although cross-linking studies and recent EPR data apparently support a model of EmrE that contains parallel dimers.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, England.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Korkhov
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Tate
mesh_terms: D017920:Antiporters / Q000737:chemistry* / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000648:ultrastructure; D017433:Protein Structure, Secondary
chemical_list: D017920:Antiporters; D029968:Escherichia coli Proteins; C075436:EmrE protein, E coli