title: Multilevel interaction of the DnaK/DnaJ(HSP70/HSP40) stress-responsive chaperone machine with the central metabolism.
abstract: Networks of molecular chaperones maintain cellular protein homeostasis by acting at nearly every step in the biogenesis of proteins and protein complexes. Herein, we demonstrate that the major chaperone DnaK/HSP70 of the model bacterium Escherichia coli is critical for the proper functioning of the central metabolism and for the cellular response to carbon nutrition changes, either directly or indirectly via the control of the heat-shock response. We identified carbon sources whose utilization was positively or negatively affected by DnaK and isolated several central metabolism genes (among other genes identified in this work) that compensate for the lack of DnaK and/or DnaK/Trigger Factor chaperone functions in vivo. Using carbon sources with specific entry points coupled to NMR analyses of real-time carbon assimilation, metabolic coproducts production and flux rearrangements, we demonstrate that DnaK significantly impacts the hierarchical order of carbon sources utilization, the excretion of main coproducts and the distribution of metabolic fluxes, thus revealing a multilevel interaction of DnaK with the central metabolism.
authors.affiliation: Laboratoire de Microbiologie et de Génétique Moléculaires, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, 118 route de Narbonne, 31062 Toulouse Cedex 9, France.|LISBP, Université de Toulouse, CNRS, INRA, INSA F-31400 Toulouse, France.
authors.forename: Fréderic
authors.initials: F
authors.lastname: Anglès
authors.affiliation: Laboratoire de Microbiologie et de Génétique Moléculaires, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, 118 route de Narbonne, 31062 Toulouse Cedex 9, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Castanié-Cornet
authors.affiliation: Laboratoire de Microbiologie et de Génétique Moléculaires, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, 118 route de Narbonne, 31062 Toulouse Cedex 9, France.
authors.forename: Nawel
authors.initials: N
authors.lastname: Slama
authors.affiliation: LISBP, Université de Toulouse, CNRS, INRA, INSA F-31400 Toulouse, France.
authors.forename: Mickael
authors.initials: M
authors.lastname: Dinclaux
authors.affiliation: Laboratoire de Microbiologie et de Génétique Moléculaires, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, 118 route de Narbonne, 31062 Toulouse Cedex 9, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Cirinesi
authors.affiliation: LISBP, Université de Toulouse, CNRS, INRA, INSA F-31400 Toulouse, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Portais
authors.affiliation: LISBP, Université de Toulouse, CNRS, INRA, INSA F-31400 Toulouse, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Létisse
authors.affiliation: Laboratoire de Microbiologie et de Génétique Moléculaires, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, 118 route de Narbonne, 31062 Toulouse Cedex 9, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Genevaux
mesh_terms: D000085:Acetates / Q000378:metabolism; D002241:Carbohydrates; D002244:Carbon / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005798:Genes, Bacterial; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D064688:Metabolic Flux Analysis; D018832:Molecular Chaperones / Q000378:metabolism*; D012808:Sigma Factor / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D000085:Acetates; D002241:Carbohydrates; C494635:DnaJ protein, E coli; D029968:Escherichia coli Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D012808:Sigma Factor; D002244:Carbon; C063842:dnaK protein, E coli