title: Emulating membrane protein evolution by rational design.
abstract: How do integral membrane proteins evolve in size and complexity? Using the small multidrug-resistance protein EmrE from Escherichia coli as a model, we experimentally demonstrated that the evolution of membrane proteins composed of two homologous but oppositely oriented domains can occur in a small number of steps: An original dual-topology protein evolves, through a gene-duplication event, to a heterodimer formed by two oppositely oriented monomers. This simple evolutionary pathway can explain the frequent occurrence of membrane proteins with an internal pseudo-two-fold symmetry axis in the plane of the membrane.
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Rapp
authors.forename: Susanna
authors.initials: S
authors.lastname: Seppälä
authors.forename: Erik
authors.initials: E
authors.lastname: Granseth
authors.forename: Gunnar
authors.initials: G
authors.lastname: von Heijne
mesh_terms: D000595:Amino Acid Sequence; D017920:Antiporters / Q000737:chemistry* / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry*; D019281:Dimerization; D019020:Directed Molecular Evolution; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics; D004996:Ethidium / Q000494:pharmacology; D019143:Evolution, Molecular; D020440:Gene Duplication; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D017920:Antiporters; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; C075436:EmrE protein, E coli; D004996:Ethidium