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Cryo-EM based theoretical model structure of transmembrane domain of the multidrug-resistance antiporter from E. coli EmrECryo-EM based theoretical model structure of transmembrane domain of the multidrug-resistance antiporter from E. coli EmrE
Structural highlights
Function[EMRE_ECOLI] Multidrug transporter that expels positively charged hydrophobic drugs across the inner membrane of E.coli., thereby conferring resistance to a wide range of toxic compounds. The drug efflux is coupled to an influx of protons. Is involved in the resistance of E.coli cells to methyl viologen, ethidium bromide and acriflavine. Is also able to transport tetraphenylphosphonium (TPP(+)) and benzalkonium.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSmall multidrug resistance (SMR) transporters contribute to bacterial resistance by coupling the efflux of a wide range of toxic aromatic cations, some of which are commonly used as antibiotics and antiseptics, to proton influx. EmrE is a prototypical small multidrug resistance transporter comprising four transmembrane segments (M1-M4) that forms dimers. It was suggested recently that EmrE molecules in the dimer have different topologies, i.e. monomers have opposite orientations with respect to the membrane plane. A 3-D structure of EmrE acquired by electron cryo-microscopy (cryo-EM) at 7.5 Angstroms resolution in the membrane plane showed that parts of the structure are related by quasi-symmetry. We used this symmetry relationship, combined with sequence conservation data, to assign the transmembrane segments in EmrE to the densities seen in the cryo-EM structure. A C alpha model of the transmembrane region was constructed by considering the evolutionary conservation pattern of each helix. The model is validated by much of the biochemical data on EmrE with most of the positions that were identified as affecting substrate translocation being located around the substrate-binding cavity. A suggested mechanism for proton-coupled substrate translocation in small multidrug resistance antiporters provides a mechanistic rationale to the experimentally observed inverted topology. Quasi-symmetry in the cryo-EM structure of EmrE provides the key to modeling its transmembrane domain.,Fleishman SJ, Harrington SE, Enosh A, Halperin D, Tate CG, Ben-Tal N J Mol Biol. 2006 Nov 17;364(1):54-67. Epub 2006 Aug 30. PMID:17005200[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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