title: Folding Optimization In Vivo Uncovers New Chaperones.
abstract: By employing a genetic selection that forces the cell to fold an unstable, aggregation-prone test protein in order to survive, we have generated bacterial strains with enhanced periplasmic folding capacity. These strains enhance the soluble steady-state level of the test protein. Most of the bacterial variants we isolated were found to overexpress one or more periplasmic proteins including OsmY, Ivy, DppA, OppA, and HdeB. Of these proteins, only HdeB has convincingly been previously shown to function as chaperone in vivo. By giving bacteria the stark choice between death and stabilizing a poorly folded protein, we have now generated designer bacteria selected for their ability to stabilize specific proteins.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Lennon
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Maike
authors.initials: M
authors.lastname: Thamsen
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Elias T
authors.initials: ET
authors.lastname: Friman
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Cacciaglia
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Sachsenhauser
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Frieda A
authors.initials: FA
authors.lastname: Sorgenfrei
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Milena A
authors.initials: MA
authors.lastname: Wasik
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: jbardwel@umich.edu.
authors.forename: James C A
authors.initials: JC
authors.lastname: Bardwell
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D019897:Periplasm / Q000737:chemistry / Q000378:metabolism*; D033902:Periplasmic Binding Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization
chemical_list: D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C429555:Ivy protein, E coli; D008074:Lipoproteins; D018832:Molecular Chaperones; C499290:OppA protein, E coli; D033902:Periplasmic Binding Proteins; C084502:hdeB protein, E coli; C066768:dppA protein, E coli; C074783:osmY protein, E coli
keywords: chaperone discovery; folding sensor; periplasm; protein folding; proteostasis