title: Nitric oxide inhibits the cochaperone activity of the RING finger-like protein DnaJ.
abstract: As a consequence of bacterial infection and the ensuing inflammation, expression of the inducible NO synthase results in prolonged synthesis of NO in high concentrations, which among other functions, contributes to the innate defense against the infectious agent. Here we show that NO inhibits the ability of the bacterial cochaperone DnaJ containing a RING finger-like domain to cooperate with the Hsp70 chaperone DnaK in mediating correct folding of denatured rhodanese. This inhibition is accompanied by S-nitrosation of DnaJ as well as by Zn2+ release from the protein. In contrast, NO has no effect on the activity of GroEL, a bacterial chaperone without zinc sulfur clusters. Escherichia coli cells lacking the chaperone trigger factor and thus relying on the DnaJ/DnaK system are more susceptible toward NO-mediated cytostasis than are wild-type bacteria. Our studies identify the cochaperone DnaJ as a molecular target for NO. Thus, an encounter of bacterial cells with NO can impair the protein folding activity of the bacterial chaperone system, thereby increasing bacterial susceptibility toward the defensive attack by the host.
authors.affiliation: Research Group Immunobiology, Medical Department of the Heinrich-Heine-University of Düsseldorf, Moorenstrasse 5, Düsseldorf, D-40225, Germany. kroencke@uni-duesseldorf.de
authors.forename: K D
authors.initials: KD
authors.lastname: Kröncke
authors.forename: H
authors.initials: H
authors.lastname: Haase
authors.forename: D
authors.initials: D
authors.lastname: Beyersmann
authors.forename: V
authors.initials: V
authors.lastname: Kolb-Bachofen
authors.forename: M K
authors.initials: MK
authors.lastname: Hayer-Hartl
mesh_terms: D002455:Cell Division / Q000187:drug effects; D018834:Chaperonin 60 / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology*; D015538:Nitrosation / Q000187:drug effects*; D017510:Protein Folding; D017384:Sequence Deletion / Q000235:genetics; D015032:Zinc / Q000378:metabolism; D016335:Zinc Fingers / Q000502:physiology
chemical_list: D018834:Chaperonin 60; C494635:DnaJ protein, E coli; D029968:Escherichia coli Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009569:Nitric Oxide; D015032:Zinc