title: Individual and collective contributions of chaperoning and degradation to protein homeostasis in E. coli.
abstract: The folding fate of a protein in vivo is determined by the interplay between a protein's folding energy landscape and the actions of the proteostasis network, including molecular chaperones and degradation enzymes. The mechanisms of individual components of the E. coli proteostasis network have been studied extensively, but much less is known about how they function as a system. We used an integrated experimental and computational approach to quantitatively analyze the folding outcomes (native folding versus aggregation versus degradation) of three test proteins biosynthesized in E. coli under a variety of conditions. Overexpression of the entire proteostasis network benefited all three test proteins, but the effect of upregulating individual chaperones or the major degradation enzyme, Lon, varied for proteins with different biophysical properties. In sum, the impact of the E. coli proteostasis network is a consequence of concerted action by the Hsp70 system (DnaK/DnaJ/GrpE), the Hsp60 system (GroEL/GroES), and Lon.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Younhee
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Departments of Chemistry and Biochemistry and Molecular Biology, University of Massachusetts-Amherst, Amherst, MA 01003, USA.
authors.forename: Kristine Faye R
authors.initials: KF
authors.lastname: Pobre
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Mathematics and Computer Science, Clarkson University, Potsdam, NY 13699, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Powers
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Kelly
authors.affiliation: Departments of Chemistry and Biochemistry and Molecular Biology, University of Massachusetts-Amherst, Amherst, MA 01003, USA. Electronic address: gierasch@biochem.umass.edu.
authors.forename: Lila M
authors.initials: LM
authors.lastname: Gierasch
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: epowers@scripps.edu.
authors.forename: Evan T
authors.initials: ET
authors.lastname: Powers
mesh_terms: D018834:Chaperonin 60 / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins; D006706:Homeostasis; D018832:Molecular Chaperones / Q000235:genetics*; D049070:Protease La / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D017510:Protein Folding; D059748:Proteolysis
chemical_list: D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C483567:Lon protein, E coli; D049070:Protease La
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