title: Proteome-wide analysis of chaperonin-dependent protein folding in Escherichia coli.
abstract: The E. coli chaperonin GroEL and its cofactor GroES promote protein folding by sequestering nonnative polypeptides in a cage-like structure. Here we define the contribution of this system to protein folding across the entire E. coli proteome. Approximately 250 different proteins interact with GroEL, but most of these can utilize either GroEL or the upstream chaperones trigger factor (TF) and DnaK for folding. Obligate GroEL-dependence is limited to only approximately 85 substrates, including 13 essential proteins, and occupying more than 75% of GroEL capacity. These proteins appear to populate kinetically trapped intermediates during folding; they are stabilized by TF/DnaK against aggregation but reach native state only upon transfer to GroEL/GroES. Interestingly, substantially enriched among the GroEL substrates are proteins with (betaalpha)8 TIM-barrel domains. We suggest that the chaperonin system may have facilitated the evolution of this fold into a versatile platform for the implementation of numerous enzymatic functions.
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kerner
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Naylor
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishihama
authors.forename: Tobias
authors.initials: T
authors.lastname: Maier
authors.forename: Hung-Chun
authors.initials: HC
authors.lastname: Chang
authors.forename: Anna P
authors.initials: AP
authors.lastname: Stines
authors.forename: Costa
authors.initials: C
authors.lastname: Georgopoulos
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Frishman
authors.forename: Manajit
authors.initials: M
authors.lastname: Hayer-Hartl
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: F Ulrich
authors.initials: FU
authors.lastname: Hartl
mesh_terms: D018835:Chaperonin 10 / Q000235:genetics / Q000378:metabolism*; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D014305:Triose-Phosphate Isomerase / Q000737:chemistry
chemical_list: D018835:Chaperonin 10; D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D020543:Proteome; C063842:dnaK protein, E coli; C403324:trigger factor, E coli; D019696:Peptidylprolyl Isomerase; D014305:Triose-Phosphate Isomerase