2I68

Cryo-EM based theoretical model structure of transmembrane domain of the multidrug-resistance antiporter from E. coli EmrE

Summary for 2I68

• Entry DOI: 10.2210/pdb2i68/pdb
• EMDB information: 1087
• Descriptor: Protein emrE (1 entity in total)
• Functional Keywords: transmembrane protein, small-multidrug resistance, transporter, homodimer, dual topology, transport protein
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane; Multi-pass membrane protein: P23895
• Total number of polymer chains: 2
• Total formula weight: 30407.42

Authors

Fleishman, S.J.,Harrington, S.E.,Enosh, A.,Halperin, D.,Tate, C.G.,Ben-Tal, N. (deposition date: 2006-08-28, release date: 2006-10-03, Last modification date: 2024-03-13)

Primary citation

Fleishman, S.J.,Harrington, S.E.,Enosh, A.,Halperin, D.,Tate, C.G.,Ben-Tal, N.
Quasi-symmetry in the Cryo-EM Structure of EmrE Provides the Key to Modeling its Transmembrane Domain
J.Mol.Biol., 364:54-67, 2006

PubMed Abstract: Small 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.

PubMed: 17005200
DOI: 10.1016/j.jmb.2006.08.072

Experimental method

ELECTRON CRYSTALLOGRAPHY (7.5 Å)