title: DnaK functions as a central hub in the E. coli chaperone network.
abstract: Cellular chaperone networks prevent potentially toxic protein aggregation and ensure proteome integrity. Here, we used Escherichia coli as a model to understand the organization of these networks, focusing on the cooperation of the DnaK system with the upstream chaperone Trigger factor (TF) and the downstream GroEL. Quantitative proteomics revealed that DnaK interacts with at least ~700 mostly cytosolic proteins, including ~180 relatively aggregation-prone proteins that utilize DnaK extensively during and after initial folding. Upon deletion of TF, DnaK interacts increasingly with ribosomal and other small, basic proteins, while its association with large multidomain proteins is reduced. DnaK also functions prominently in stabilizing proteins for subsequent folding by GroEL. These proteins accumulate on DnaK upon GroEL depletion and are then degraded, thus defining DnaK as a central organizer of the chaperone network. Combined loss of DnaK and TF causes proteostasis collapse with disruption of GroEL function, defective ribosomal biogenesis, and extensive aggregation of large proteins.
authors: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors: Giulia
authors: G
authors: Calloni
authors: Taotao
authors: T
authors: Chen
authors: Sonya M
authors: SM
authors: Schermann
authors: Hung-Chun
authors: HC
authors: Chang
authors: Pierre
authors: P
authors: Genevaux
authors: Federico
authors: F
authors: Agostini
authors: Gian Gaetano
authors: GG
authors: Tartaglia
authors: Manajit
authors: M
authors: Hayer-Hartl
authors: F Ulrich
authors: FU
authors: Hartl
mesh_terms: D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D017353:Gene Deletion; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D020543:Proteome; C063842:dnaK protein, E coli