title: Liberation of the intramolecular interaction as the mechanism of heat-induced activation of HSP90 molecular chaperone.
abstract: The molecular chaperone function of HSP90 is activated under heat-stress conditions. In the present study, we investigated the role of the interactions in the heat-induced activation of HSP90 molecular chaperone. The preceding paper demonstrated two domain-domain interactions of HtpG, an Escherichia coli homologue of mammalian HSP90, i.e. an intra-molecular interaction between the N-terminal and middle domains and an intermolecular one between the middle and C-terminal domains. A bacterial two-hybrid system revealed that the two interactions also existed in human HSP90alpha. Partners of the interaction between the N-terminal and middle domains of human HSP90alpha could, but those between the middle and C-terminal domains could not, be replaced by the domains of HtpG. Thus, the interface between the N-terminal and middle domains is essentially unvaried from bacterial to human members of the HSP90-family proteins. The citrate synthase-binding activity of HtpG at an elevated temperature was solely localized in the N-terminal domain, but HSP90alpha possessed two sites in the N-terminal and other domains. The citrate-synthase-binding activity of the N-terminal domain was suppressed by the association of the middle domain. The complex between the N-terminal and middle domains is labile at elevated temperatures, but the other is stable even at 70 degrees C. Taken together, we propose the liberation of the N-terminal client-binding domain from the middle suppressor domain is involved in the temperature-dependent activation mechanism of HSP90 molecular chaperone.
authors.affiliation: Department of Oral Biochemistry, Nagasaki University School of Dentistry, Nagasaki, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Tanaka
authors.forename: T K
authors.initials: TK
authors.lastname: Nemoto
authors.forename: T
authors.initials: T
authors.lastname: Ono
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D002950:Citrate (si)-Synthase / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D008954:Models, Biological; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013552:Swine; D013816:Thermodynamics; D020798:Two-Hybrid System Techniques
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D018841:HSP90 Heat-Shock Proteins; C489352:HtpG protein, E coli; D011994:Recombinant Proteins; C066720:HtpG protein, bacteria; D002950:Citrate (si)-Synthase